Influence of airspace geometry and surfactant on the retention of man-made vitreous fibers (MMVF 10a). (Research).
Inhaled and deposited man-made vitreous vitreous /vit·re·ous/ (vit´re-us)
1. glasslike or hyaline.
2. vitreous body.
primary persistent hyperplastic vitreous fibers (MMVF (MultiMedia Video File) See MVDisc. ) 10a (low-fluorine preparation of Schuller 901 insulation glass) were studied by electron microscopy in hamster lungs, fixed by intravascular intravascular /in·tra·vas·cu·lar/ (in?trah-vas´ku-lar) within a vessel.
Within one or more blood vessels. perfusion within 23 [+ or -] 2 min (SD) of the initial inhalation. We found fibers on the surfaces of conducting airways and alveoli Alveoli
Small air sacs or cavities in the lung that give the tissue a honeycomb appearance and expand its surface area for the exchange of oxygen and carbon dioxide. . In the airways, 89% of the fibers were totally and 11% partially covered by lining-layer material. In the alveoli, 32% of the fibers were totally submersed; others touched the alveolar alveolar /al·ve·o·lar/ (al-ve´o-lar) [L. alveolaris ] pertaining to an alveolus.
Relating to an alveolus. wall, stuck at one end, bridging the airspace. Studies in a surface balance showed that fibers were immersed into the aqueous subphase by approximately 50% at film surface tensions of 20-25 mJ/[m.sup.2] and were submersed (totally immersed; i.e., totally surrounded by fluid) at approximately 10 mJ/[m.sup.2]. Fibers were also found to be phagocytosed by macrophages Macrophages
White blood cells whose job is to destroy invading microorganisms. Listeria monocytogenes avoids being killed and can multiply within the macrophage. . We found a substantial number of particle profiles within alveolar blood capillaries. Fiber length and alveolar geometry appear to be important limiting factors for the submersion submersion
the act of placing, or the condition of being under, the surface of a liquid. of vitreous fibers into the lungs' surface lining layer. Key words: aerosol, airways, alveoli, deposition, hamster, man-made vitreous fibers, surface balance, surface forces, surfactant Surfactant Definition
Surfactant is a complex naturally occurring substance made of six lipids (fats) and four proteins that is produced in the lungs. It can also be manufactured synthetically. .
Man-made vitreous fibers (MMVF) are inorganic amorphous fibers made from glass, rock, clay, slag, or pure oxide raw material. They are used primarily for thermal and acoustic insulation. The fact that asbestos fibers are carcinogenic carcinogenic
having a capacity for carcinogenesis. has led to the fear that the inhalation of vitreous fibers, which have similar size and shape, poses a serious risk to human health. The mechanisms by which fibers induce lung disease lung disease Pulmonary disease Pulmonology Any condition causing or indicating impaired lung function Types of LD Obstructive lung disease–↓ in air flow caused by a narrowing or blockage of airways–eg, asthma, emphysema, chronic bronchitis; are still not completely understood. The potential toxicity of a given type of fiber is determined by dimension, durability, and fiber dose in lungs (Port and Friedrichs 1972; Stanton and Wrench 1972). Broad ranges of inhalation studies with different fiber types have been performed and have been extensively reviewed by Hesterberg and Hart (2001). A strong relationship between biopersistence of the fiber and pathogenicity in lungs has been reported (Hesterberg et al. 1998; Kamstrup et al. 1998). Most of the tested vitreous fibers were less biopersistent and caused less pathogenicity than asbestos fibers.
Despite numerous studies with reference to pathogenicity, little is known about how inhaled vitreous fibers interact with the inner surface of the lungs immediately after their deposition. Knowledge about the mechanisms of fiber retention is important with respect to the clearance of vitreous fibers and their possible risk to human health.
The surface-lining layer in lungs consists of an aqueous phase aqueous phase
The water portion of a system consisting of two liquid phases, one that is primarily water and a second that is a liquid immiscible with water. and a surfactant film at the air-liquid interface. The continuous aqueous layer adjacent to the epithelial cells Epithelial cells
Cells that form a thin surface coating on the outside of a body structure.
Mentioned in: Corneal Transplantation has a relatively low viscosity. The existence, thickness, and continuity of a gel phase above this periciliary layer in the various airway compartments and species have been disputed. In small airways small airways A term for membranaceous bronchioles–noncartilaginous conducting airways with a fibromuscular wall and respiratory bronchioles–airways in which the fibromuscular wall is partially alveolated. See Small airways disease. , a thick mucus layer has never been found (Geiser et al. 1997; Gil and Weibel 1971). The surfactant film at the air-liquid interface covers the aqueous phase and it is--based on all available evidence--continuous between the alveoli and central airways (Geiser et al. 1997; Gil and Weibel 1971; Im Hof et al. 1997).
Studies in vitro in vitro /in vi·tro/ (in ve´tro) [L.] within a glass; observable in a test tube; in an artificial environment.
In an artificial environment outside a living organism. have shown that the surfactant promotes the displacement of polystyrene particles from air into an aqueous subphase, whereby the extent of immersion depends on the surface tension of the surfactant film (Gehr et al. 1990; Schurch et al. 1990, 1993): the lower the surface tension, the greater the immersion. Furthermore, there is evidence from animal studies for the displacement of a variety of spherical particles in lungs (Geiser et al. 2000a, 2000b, 2000c). The influence of the shape of particles on their immersion into the aqueous lining layer is largely unknown.
A surface tension of 32 mJ/[m.sup.2] was measured in the trachea trachea (trā`kēə) or windpipe, principal tube that carries air to and from the lungs. It is about 4 1-2 in. (11.4 cm) long and about 3-4 in. (1.9 cm) in diameter in the adult. of horses (Im Hof et al. 1997), and values for expiration in alveoli were below 2 mJ/[m.sup.2] (Schurch et al. 1985). Very recently, evidence for surface tension values Surface tension values for some interfaces at the indicated temperatures. Note that the SI units millinewtons per meter (mN·m–1) are equivalent to the cgs units, dynes per centimetre (dyn·cm–1). below 15 mJ/[m.sup.2] in the intrapulmonary conducting airways was obtained from particle deposition studies in hamsters (Geiser et al. 2000c). It is not known how different surface tension values would influence the displacement of fibers into the lining layer. The immersion of fibers into the surface-lining layer and their displacement toward the epithelium by surfactant may have consequences for fiber dissolution and/or for the clearance pathway of fibers.
To evaluate the distribution of fibers within lungs immediately after their deposition, inhaled and deposited MMVF 10a were studied in hamsters by electron microscopy. The immersion of fibers, promoted by a surfactant film formed on an aqueous substrate, was assessed in a surface balance by light microscopy.
Materials and Methods
Fibers. MMVF 10a were kindly provided by Philippe Thevenaz (Research and Consulting Company, Fullinsdorf, Switzerland). They have a smooth surface and are mostly straight cylinders (Figure 1).
[FIGURE 1 OMITTED]
To estimate the surface free energy of the glass fibers used in this study, we measured the contact angle of dibutyl phthalate droplets (surface tension, 34.5 mJ/[m.sup.2] at 22[degrees]C) placed on glass slides cleaned with chromic acid chromic acid /chro·mic ac·id/ the common name for chromium trioxide (CrO3), although the term strictly refers to the species H2CrO4, which exists only in aqueous solution. It is a highly toxic, corrosive, strong oxidizing agent.
1. at different time points after exposure to laboratory air. The contact angle of dibutyl phthalate droplets on glass was compared with that obtained on a polystyrene substrate with the same fluid. In addition, the solid-vapor free energy was estimated by using the equation of state approach (Spelt and Li 1996). The equation of state helps determine the solid-vapor interfacial energy from the measured contact angle that a test fluid droplet droplet
very small drop of fluid.
the finite particles of matter which are transmitted from animal to animal. of a known surface tension makes on a solid substrate.
Animals, aerosol generation, and inhalation. Inhaled and deposited fibers were studied in male Syrian Golden hamsters [n = 4; AURA, HanIbm:AURA (specific-pathogen free); Biological Research Laboratories Ltd., Fullinsdorf, Switzerland] weighing 132-163 g. The animals, aerosol generation, and inhalation have been described in detail previously (Geiser et al. 2000a; Im Hof et al. 1989; Waber et al. 1999). Briefly, aerosols were generated by jet nebulization nebulization /neb·u·li·za·tion/ (neb?u-li-za´shun)
1. conversion into an aerosol or spray.
2. treatment by an aerosol. of droplets of suspensions of MMVF 10a fibers (2 mg/mL in 100% ethanol) into a particle-free air stream. The fibers were then dried, charge equilibrated, and concentrated before being injected into a reservoir and transferred to the inhalation/exhalation channel. The deeply anesthetized a·nes·the·tize also a·naes·the·tize
tr.v. a·nes·the·tized, a·nes·the·tiz·ing, a·nes·the·tiz·es
To induce anesthesia in.
a·nes and completely relaxed hamsters inhaled the aerosol directly from the reservoir through an intratracheal cannula cannula /can·nu·la/ (kan´u-lah) a tube for insertion into a vessel, duct, or cavity; during insertion its lumen is usually occupied by a trocar.
can·nu·la or can·u·la
n. pl. during continuous negative-pressure ventilation. They were ventilated ven·ti·late
tr.v. ven·ti·lat·ed, ven·ti·lat·ing, ven·ti·lates
1. To admit fresh air into (a mine, for example) to replace stale or noxious air.
2. with a tidal volume tidal volume
The volume of air inspired or expired in a single breath during regular breathing. Also called tidal air.
n ([V.sub.T]) of 0.95 [+ or -] 0.06 mL (mean [+ or -] SD)--maintained at 70-80% of total lung capacity--and a breathing frequency (f) of 61 [+ or -] 1 breath/min (mean [+ or -] SD), which equals slow, deep breathing (Inglis 1980). The breathing parameters and the number of inhaled and exhaled fibers were measured by pneumotachography pneumotachography
the science of using a pneumotachograph. and laser-light scattering photometry photometry (fōtŏm`ətrē), branch of physics dealing with the measurement of the intensity of a source of light, such as an electric lamp, and with the intensity of light such a source may cast on a surface area. . Because the fibers used in this study were heterogeneous in size, number estimates are of directional value only. Aerosols were inhaled for 5-12 min, until a sufficient number of fibers for microscopic analysis were deposited. Immediately thereafter, the lungs were prepared for intravascular perfusion fixation.
We collected aerosol samples on filters and analyzed the fiber size distribution (Figure 2). The average length of 200 fibers measured by light microscopy was 16 [+ or -] 13 [micro]m (mean [+ or -] SD; range, 1-66 [micro]m); the average diameter was 1.1 [+ or -] 0.2 [micro]m (range, 0.6-1.7 [micro]m). The average length-to-diameter ratio was 15.6 [+ or -] 13.3 (range, 1.1-64.0). Twenty fibers had a length-to-diameter ratio of < 3; hence, the particulate fraction of MMVF 10a in the aerosol was 10%.
[FIGURE 2 OMITTED]
Lung fixation. Whole lungs can be preserved for morphologic analysis by the introduction of a suitable fixative fixative /fix·a·tive/ (fik´sit-iv) an agent used in preserving a histological or pathological specimen so as to maintain the normal structure of its constituent elements.
adj. into the airways of a collapsed lung or by delivery of the fixatives to the lungs via the blood vessels Blood vessels
Tubular channels for blood transport, of which there are three principal types: arteries, capillaries, and veins. Only the larger arteries and veins in the body bear distinct names. (Weibel 1984). The instillation of aqueous fixative solutions into the airways is not suitable for the investigation of the inner surface of the lungs because the surface-lining layer and all its cellular and acellular acellular /acel·lu·lar/ (a-sel´u-ler) not cellular in structure.
1. Containing no cells; not made of cells.
2. Devoid of cells; noncellular. constituents are dislocated dis·lo·cate
tr.v. dis·lo·cat·ed, dis·lo·cat·ing, dis·lo·cates
1. To put out of usual or proper place, position, or relationship.
2. from their native positions and transferred to other regions of the organ (Brain et al. 1984). Instillation of airways with nonpolar nonpolar
not having poles; not exhibiting dipole characteristics. fixative solutions (1% osmium tetroxide dissolved in perfluorocarbon) has been demonstrated to preserve the aqueous lining layer and especially also the surfactant film at the air-liquid interface (Geiser et al. 1997; Lee et al. 1995; Sims et al. 1991; Thurston et al. 1976). However, it is not known whether material that is not submersed in the surface-lining layer may be dislocated by this procedure.
Because it was the aim of this study to investigate the location of deposited fibers with respect to the inner surface of the lungs, the fixative solutions were applied by vascular perfusion via the pulmonary artery pulmonary artery
n. Abbr. PA
1. An artery that enters the hilus of the right lung, with branches distributed with the bronchi; right pulmonary artery.
2. , which allows the airways and alveoli to remain in their natural air-filled state. Sequential intravascular perfusion of buffered 2.5% glutaraldehyde glutaraldehyde /glu·ta·ral·de·hyde/ (gloo?tah-ral´de-hid) a disinfectant used in aqueous solution for sterilization of non-heat–resistant equipment; also used as a tissue fixative for light and electron microscopy. , 1% osmium tetroxide, and 0.5% uranyl acetate (Bachofen et al. 1982; Im Hof et al. 1989; Weibel 1984) has been shown to well preserve the surface-lining layer with its phagocytic cells Phagocytic cells
A cell that ingests microorganisms and foreign particles.
Mentioned in: Chronic Granulomatous Disease and the surfactant film at the air-liquid interface of intrapulmonary conducting airways and alveoli in laboratory animals (Geiser et al. 1997; Gil and Weibel 1969, 1971).
All lungs were fixed within 23 [+ or -] 2 min of the initial inhalation. The short time between inhalation and lung fixation allows the investigation of fibers as close as possible to where they were deposited. After fixation, the lungs were removed from the thorax thorax, body division found in certain animals. In humans and other mammals it lies between the neck and abdomen and is also called the chest. The skeletal frame of the thorax is formed by the sternum (breastbone) and ribs in front and the dorsal vertebrae in back. and split into left lung, right lung, and accessory lobe (Geiser et al. 1990).
Tissue processing for microscopic analysis. The lung lobes were cut perpendicularly to the longitudinal axis into series of thick (3 mm) and thin (1.5 mm) slices, with random start (Geiser et al. 1990). The thin slices were used for electron microscopy, and the thicker ones for other purposes. A total of 49 thin slices were sampled for transmission electron microscopy “TEM” redirects here. For other uses, see TEM (disambiguation).
Transmission electron microscopy (TEM) is an imaging technique whereby a beam of electrons is transmitted through a specimen, then an image is formed, magnified and directed to appear either (TEM TEM
1. transmission electron microscope.
3. transmissible encephalopathy of mink. ) and further cut into cubes of about 1 mm side length. These tissue blocks (n = 144) were dehydrated de·hy·drate
v. de·hy·drat·ed, de·hy·drat·ing, de·hy·drates
1. To remove water from; make anhydrous.
2. To preserve by removing water from (vegetables, for example). in ethanol and embedded in Epon (Im Hof et al. 1989). Ultrathin sections, stained with uranyl acetate and lead citrate citrate /cit·rate/ (sit´rat) a salt of citric acid.
citrate phosphate dextrose (CPD) anticoagulant citrate phosphate dextrose solution. , were examined with a Philips 300 transmission electron microscope electron microscope: see microscope. (Philips AG, Zurich, Switzerland) operating at 60 kV.
For scanning electron microscopic (SEM) analysis, a total of 15 thin slices were sampled, dehydrated in ethanol, critical-point-dried, and sputter-coated with platinum. They were examined with a Philips XL 30-FEG scanning electron microscope scan·ning electron microscope
n. Abbr. SEM
An electron microscope that forms a three-dimensional image on a cathode-ray tube by moving a beam of focused electrons across an object and reading both the electrons scattered by the object and (Philips) operating at 10 kV. Length and diameter of all registered fibers were measured by SEM.
Displacement of MMVF 10a in the Langmuir-Wilhelmy balance. The displacement of MMVF 10a fibers into an aqueous substrate by a surfactant film was investigated with a monolayer mon·o·lay·er
1. A film or layer one molecule thick formed at the interface between water and either oil or air by a substance such as a partially esterified fatty acid that contains both hydrophobic and hydrophilic groups in the same of 1,2-dipalmitoyl-sn-3-glycerophosphatidylcholine (DPPC DPPC Dipalmitoyl Phosphatidylcholine (lung surfactant)
DPPC Disabled Persons Protection Commission (Massachusetts)
DPPC Disaster Preparedness and Prevention Commission
DPPC Deployable Print Production Center ; Sigma-Aldrich Canada Ltd., Oakville, Ontario, Canada) in a Langmuir-Wilhelmy surface balance (our own design). The DPPC monolayer was spread from a solution of 2 mg/mL in ethanol onto an aqueous substrate of a solution of 0.9% NaCl and 40% sucrose (density, 1.25 g/mL). The monolayer was spread within an area of 25 [cm.sup.2] enclosed by a Teflon ribbon supported by a rhombic rhom·bic
1. Relating to the rhombencephalon.
2. Rhomboid. frame (Schoedel et al. 1969). Our objective was to assess the displacement of glass fibers at surface tensions between 30 and 5 mJ/[m.sup.2]. Pulling the rhombic frame to an elongated e·lon·gate
tr. & intr.v. e·lon·gat·ed, e·lon·gat·ing, e·lon·gates
To make or grow longer.
adj. or elongated
1. Made longer; extended.
2. Having more length than width; slender. shape reduced the surface tension of the DPPC film, and the surface tension force was measured by a platinum Wilhelmy plate connected to an electrobalance.
After adjustment of the monolayer surface tension to a preset value, the glass dish was placed onto a microscope stage and fibers were blown onto the monolayer. The fibers were then observed and photographed with a Nikon Optiphot metallurgical microscope (Nikon, Mississauga, Ontario, Canada), equipped for differential interference contrast and dark field for epi-illumination.
Fibers retained on the surfaces of airways and alveoli: SEM analysis. The analysis by SEM allowed the investigation of fibers on airway and alveolar surfaces. Single fibers and small aggregates were found. Larger aggregates were observed at bifurcations. In the intrapulmonary conducting airways, 89% of the fibers were found to be completely covered by surface-lining layer material, and 11% were only partially covered (Figures 3 and 4). The average length and diameter of the fibers in the airways were 37.3 [+ or -] 19.4 [micro]m (mean [+ or -] SD; range, 7-104 [micro]m) and 1.1 [+ or -] 0.4 [micro]m (range, 0.3-2 [micro]m), respectively (Figure 5). The average length-to-diameter ratio was 34.0 [+ or -] 19.0 (range, 7-122).
[FIGURES 3-5 OMITTED]
In the alveoli, 32% of the fibers were completely covered, 26% were partially, and 42% were not covered not covered Health care adjective Referring to a procedure, test or other health service to which a policy holder or insurance beneficiary is not entitled under the terms of the policy or payment system–eg, Medicare. Cf Covered. by the lung-lining layer (Figures 3 and 6). Some fibers appeared to project into the alveolar airspace or to cross it, and they touched the alveolar surface only with their ends. The average length and diameter of the fibers in the alveoli were 20.9 [+ or -] 8.3 [micro]m (range, 9-35 [micro]m) and 0.9 [+ or -] 0.3 [micro]m (range, 0.5-1.5 [micro]m), respectively (Figure 5). The average length-to-diameter ratio was 27.8 [+ or -] 14.0 (range, 10-52).
[FIGURE 6 OMITTED]
Fiber retention in lungs by TEM. The analysis by TEM allowed the investigation of fibers within the entire lung tissue. Because with this method we analyzed two-dimensional transects of the fibers in tissue sections, we could observe the traces of cut cylinders, which were in all cases either circles or ellipses Ellipses is the plural form of either of two words in the English language:
From the 144 embedded tissue blocks, 96 contained intrapulmonary conducting airways as well as lung parenchyma Parenchyma
A ground tissue of plants chiefly concerned with the manufacture and storage of food. The primary functions of plants, such as photosynthesis, assimilation, respiration, storage, secretion, and excretion—those associated with living , and these were used for analysis by TEM. A total of 335 MMVF 10a profiles, which are electron-dense and easy to recognize, were analyzed on micrographs of ultrathin sections (Table 1). We found 35 mostly fiber profiles in the conducting airways, and we registered 69 profiles in the alveoli, about half of them originating from fibers and the other half from particles. Eight fibers and/or particles were found to be phagocytosed by airway macrophages (Figure 7B), and nine by alveolar macrophages (Figure 8C). We observed 228 mostly particle profiles in the lumen of alveolar blood capillaries, and 1 within a pulmonary artery. One fiber profile was found within a type I epithelial cell, and the location of another one could not be identified. Neither fiber nor particle profiles were found in the interstitium.
[FIGURES 7-8 OMITTED]
In airways, 96% of the profiles were submersed in the surface-lining layer, whereas 4% appeared not to be covered by any material (Figures 3 and 7A). In alveoli, 33% of the profiles were found to be completely, 13% partially, and 54% not covered by any surface-lining layer material (Figures 3, 8A, and 8B). The profiles found in the lumina of blood vessels had blank surfaces (Figure 8D).
Displacement of fibers into an aqueous substrate by a surfactant film. The experiments in the Langmuir-Wilhelmy surface balance demonstrated that the extent of fiber immersion into the aqueous phase depends on the surface tension of the film at the air-liquid interface. At 30 mJ/[m.sup.2], < 10% of the fibers were submersed into the aqueous substrate, whereas at surface tensions < 20 mJ/[m.sup.2], almost all fibers (> 95%) were completely submersed (Figure 9). However, the displacement of fibers was found to depend also on size. Fibers shorter than 10 [micro]m were immersed into the aqueous subphase by approximately 50% at 25-30 mJ/[m.sup.2] and were completely submersed at [less than or equal to] 20 mJ/[m.sup.2]. Fibers with a length of 20-30 [micro]m were immersed to 50% at a surface tension of 15 mJ/[m.sup.2] and to 95% at [less than or equal to] 10 mJ/[m.sup.2].
[FIGURE 9 OMITTED]
Surface free energy of glass fibers. The surface free energy of clean glass is several hundred millijoules per square meter. However, glass surfaces adsorb adsorb /ad·sorb/ (ad-sorb´) to attract and retain other material on the surface; to conduct the process of adsorption.
To take up by adsorption. impurities (materials) suspended in the ambient air, which considerably reduces the surface free energy value of glass. Measurements on surfaces of glass slides have demonstrated that clean glass, after exposure for 15-20 hr to laboratory air, has a surface free energy dose to that of polystyrene (i.e., ~ 35 mJ/[m.sup.2]). We therefore expect that the glass fibers investigated in the anatomy laboratory in Bern had surface free energies similar to that of polystyrene.
The microscopic analyses of inhaled and deposited MMVF 10a in hamster lungs described here show that in the conducting airways almost all fibers were submersed in the aqueous lining layer, whereas in the alveoli only about one-third of the fibers were completely covered by lining layer material. It has been shown previously that the displacement of polystyrene microspheres depends on the surface tension of the surfactant film at the air-liquid interface (Gehr et al. 1990; Schurch et al. 1990, 1993). The lower the film surface tension, the greater the extent of particle immersion into the aqueous subphase. The extent of immersion as assessed in the Langmuir-Wilhelmy surface balance demonstrated that immersion of MMVF 10a into the subphase by approximately 50% occurred for fibers shorter than 10 [micro]m at film surface tensions of 25 mJ/[m.sup.2] and for those 20-30 [micro]m in length at 15 mJ/[m.sup.2]. For submersion of the longer fibers, the film surface tension had to be [less than or equal to] 10 mJ/[m.sup.2].
The calculation of the forces that are exerted on cylindrical MMVF 10a after their deposition on a liquid surface is somewhat more difficult than that for forces exerted on microspheres, because of the complex wetting behavior. First, fibers have infinite possibilities with respect to their orientation of hitting a liquid surface. Second, MMVF 10a have variable dimensions and are straight or bent cylinders, meaning that forces exerted on them would have to be calculated for each single fiber. Third, the surface chemistry of the glass fibers does not seem to be homogeneous, in that the three-phase line (the line where the vapor, fluid, and solid phases join) appears to be corrugated cor·ru·gate
v. cor·ru·gat·ed, cor·ru·gat·ing, cor·ru·gates
To shape into folds or parallel and alternating ridges and grooves.
v.intr. . This can be observed by light microscopy, especially on long fibers; dry spots (not wetted by the surfactant film) are followed by partially immersed parts, and so on, (Figure 10). From the model experiments in the Langmuir-Wilhelmy surface balance, it follows that glass fibers (MMVF 10a) are displaced into the aqueous lung-lining layer only below a film surface tension of 20 mJ/[m.sup.2]. Assuming that clean glass has a surface free energy of several hundred millijoules per square meter, one would expect immediate wetting and submersion of glass fibers caused by a surfactant film of a surface free energy of approximately 25 mJ/[m.sup.2]. However, glass surfaces tend to adsorb impurities (materials) suspended in the ambient air, such that the surface free energy of the fibers used in this study is expected to be considerably lower. As a consequence, we observed that such fibers are wetted and displaced only if the film surface tension falls below approximately 30 mJ/[m.sup.2], which is consistent with a reduced surface free energy of the glass due to adsorption adsorption, adhesion of the molecules of liquids, gases, and dissolved substances to the surfaces of solids, as opposed to absorption, in which the molecules actually enter the absorbing medium (see adhesion and cohesion). of impurities.
[FIGURE 10 OMITTED]
According to microscopic analysis, about 90% of the glass fibers were submersed in the surface-lining layer in the intrapulmonary conducting airways. In this lung compartment, fiber length seemed not to be a limiting factor for their displacement, because fibers up to 104 lam in length were found to be submersed. The in vitro experiments demonstrated that in order to promote total immersion of glass fibers of a length of 20-30 [micro]m, the film surface tension has to fall to approximately 10 mJ/[m.sup.2]. This value is considerably below the surface tension of 32 mJ/[m.sup.2] measured in the trachea of horses (Im Hof et al. 1997) and substantially below the equilibrium surface tension of approximately 25 mJ/[m.sup.2] for pulmonary surfactant films. Because surface tensions < 22-25 mJ/[m.sup.2] can only be achieved by mechanically compressed films, the conclusion is that the surfactant film reaches at least temporarily a compressed state in the intrapulmonary conducting airways of hamsters. Because the alveolar surfactant film reaches minimum surface tensions below approximately 2 mJ/[m.sup.2] under in vivo in vivo /in vi·vo/ (ve´vo) [L.] within the living body.
Within a living organism.
in vivo adv. conditions (Bachofen et al. 1987), it is clear that there must be a surface tension gradient between the compressed alveolar surfactant film and that in the trachea or large bronchi bronchi /bron·chi/ (brong´ki) plural of bronchus.
Two main branches of the trachea that go into the lungs. This then further divides into the bronchioles and alveoli. , but the definition of the gradient remains unclear.
Direct surface tension measurements in the small airway compartments have not been possible so far with current techniques because these airways are not accessible. However, indirect evidence for surface tensions far below the equilibrium value of approximately 25 mN/m in the central airways of rabbits has recently been obtained by Bachofen and Schurch (2001), who demonstrated that the shape of bronchiolar bronchiolar
pertaining to or emanating from the bronchioles.
see pulmonary neoplasm. macrophages beneath the surfactant film in the surface-lining layer depends on the local surface tension. The shape of the macrophages, determined by TEM, may serve in turn to estimate the airway surface tension at that location.
Because the surface tension in the alveoli reaches values < 2 mJ/[m.sup.2] on expiration, one would expect all of the fibers in the alveoli to be completely submersed in the surface-lining layer. However, in the present study, we found that about one-third of the fibers in alveoli were not covered by the surface-lining layer. This may be due to geometric limitations. The geometry of alveoli in hamsters resembles spherical cavities with an average diameter of about 80 [micro]m (Kennedy et al. 1978). Long fibers may touch the inner surface with the tips of both ends and bridge the alveolar airspace. Such configurations have been observed (Rogers et al. 1999). The fibers are immersed into the lining layer only at their ends. Therefore, partial coverage of fibers by lung lining material as observed by SEM may be explained by size and geometry of the fibers and the airspaces.
Dissolution of the fibers becomes possible after their displacement into the aqueous lining layer. In addition, it is likely that surfactant components or proteins are adsorbed onto the surfaces of the fibers, which may alter their clearance pathway or their toxicologic potency.
The displacement of fibers into the surface-lining layer brings them into close contact with resident macrophages, which comprise a major clearance pathway for particles deposited in the alveoli and in small airways (Geiser et al. 1990, 2000a, 2000b). In addition, the displacement of fibers toward the epithelium may facilitate particle uptake by epithelial cells and eventually translocation translocation /trans·lo·ca·tion/ (trans?lo-ka´shun) the attachment of a fragment of one chromosome to a nonhomologous chromosome. Abbreviated t. to interstitial and endothelial endothelial /en·do·the·li·al/ (-the´le-al) pertaining to or made up of endothelium.
A layer of cells that lines the inside of certain body cavities, for example, blood vessels. sites, which may have consequences for causing lung disease.
In the present study, about two-thirds of all vitreous glass profiles were found in the lumen of alveolar blood capillaries. The majority of these profiles had irregular shapes and angular surfaces and most likely represents particles originating from broken fibers. The particulate fraction of MMVF 10a in the aerosol was 10%. Such particles are in a size range to reach the alveoli by inhalation and to be deposited there. This is demonstrated by the observation that many more particle profiles were found in the alveolar than in the airway compartment. Currently, it is not known how the MMVF 10a particles entered the capillary lumen. There are several mechanisms by which particles can be displaced from one tissue compartment to another one. First, particles < 1 [micro]m in diameter or those persisting on lung surfaces have been shown to be taken up more readily by epithelial cells (Ferin et al. 1992; Mossmann et al. 1978) or to be translocated even to interstitial and endothelial sites (Oberdorster et al. 1996). We found only one vitreous glass profile within the interalveolar septum in·ter·al·ve·o·lar septum
The close-meshed capillary network covered by thin alveolar epithelial cells that intervenes between adjacent pulmonary alveoli. , within a type I epithelial cell. Therefore, clearance of MMVF 10a through the epithelial cells and further translocation via the interstitium and endothelial cells into the lumen of blood capillaries is unlikely. This is consistent with observations of Brody et al. (1981), who showed that for minute asbestos fibrils in rats, the above-mentioned sequence of particle transport had occurred only 4 or more days after exposure. In contrast, in the present study, < 1 hr elapsed e·lapse
intr.v. e·lapsed, e·laps·ing, e·laps·es
To slip by; pass: Weeks elapsed before we could start renovating.
n. between the onset of the inhalation until lung fixation. Second, mechanical translocation (e.g., due to the formation of a pneumothorax pneumothorax (nmōthôr`ăks), collapse of a lung with escape of air into the pleural cavity between the lung and the chest wall. The cause may be traumatic (e.g. ) is another mechanism by which intact or broken fibers may have entered the blood circulation. Asbestos and glass fibers piercing the air-blood barrier have been demonstrated by others (Lee et al. 1979; Rogers et al. 1999). In the present study, this might have happened upon pneumothorax formation, but we did not see ruptured tissue near to the location where we found fibers. Finally, particles may be driven through the cell membranes, for example, through those of the type I epithelial cells, by interfacial forces (adhesive interactions). We demonstrated in a recent study (Rothen et al. In press) that particles < 1 [micro]m in diameter are able to penetrate the cell membrane of erythrocytes Erythrocytes
Red blood cells.
Mentioned in: Bartonellosis
n.pl red blood cells. by nonspecific nonspecific /non·spe·cif·ic/ (non?spi-sif´ik)
1. not due to any single known cause.
2. not directed against a particular agent, but rather having a general effect.
1. mechanisms. These observations are consistent with those made by Rimai et al. (2000), who showed that spherical glass particles in the micrometer micrometer (mīkrŏm`ətər, mī`krōmē'tər).
1 Instrument used for measuring extremely small distances. size range are driven into a polystyrene substrate by adhesive interactions. For example, glass particles 4 [micro]m in radius become engulfed by the substrate by approximately 90%, whereas particles 10 [micro]m in radius become substantially less engulfed. These investigators discussed the possibility of total engulfment en·gulf
tr.v. en·gulfed, en·gulf·ing, en·gulfs
To swallow up or overwhelm by or as if by overflowing and enclosing: The spring tide engulfed the beach houses. of relatively hard and small particles by a softer substrate.
Nevertheless, if the particulate fraction of MMVF 10a is cleared by the blood circulation, organs beyond the lungs should be carefully investigated after fiber exposure. Marsh et al. (1990) reported a significant increase in mortality for nephritis nephritis (nəfrī`təs), inflammation of the kidney. The earliest finding is within the renal capillaries (glomeruli); interstitial edema is typically followed by interstitial infiltration of lymphocytes, plasma cells, eosinophils, and a and nephrosis nephrosis (nəfrō`səs), kidney disease characterized by lesions of the epithelial lining of the renal tubules, resulting in marked disturbance in the filtration function and the consequent appearance of large amounts of protein (albumin) in the 1985 follow-up study of workers exposed to man-made mineral fibers. Sali et al. (1999) suggested the possibility of an increased risk of nonmalignant renal disease with duration of employment in a nonneoplastic mortality study of European workers who produced rock or slag wool. Moreover, they demonstrated that mortality from ischemic heart disease Ischemic heart disease
Insufficient blood supply to the heart muscle (myocardium).
Mentioned in: Myocarditis
ischemic heart disease was increased in workers exposed to rock or slag wool and in continuous-filament workers. Yet, Sjogren (2000) suggested that the increased mortality from ischemic heart disease originates from the high concentration of fibrinogen Fibrinogen
The major clot-forming substrate in the blood plasma of vertebrates. Though fibrinogen represents a small fraction of plasma proteins (normal human plasma has a fibrinogen content of 2–4 mg/ml of a total of 70 mg protein/ml), its conversion caused by the low-grade inflammation after fiber inhalation, and Chiazze et al. (1999) did not find any association between respirable respirable /res·pir·a·ble/ (re-spir´ah-b'l)
1. suitable for respiration.
2. small enough to be inhaled.
1. Fit for breathing, as air. fibers and nephritis or nephrosis in a case-control study on Caucasians who worked in glass wool production plants.
The observation that fibers were preferentially deposited at bifurcations in airways and alveoli has also been reported for inhalation studies using other fiber types (Brody et al. 1981; Brody and Roe 1983; Rogers et al. 1999).
In summary, the present study shows that glass fibers are displaced by a surfactant film and immersed into the aqueous lining layer in airways and alveoli, if the surface tension reaches [less than or equal to] 10 mJ/[m.sup.2], provided that the fibers come into contact with the inner surface of the lung. The geometry and dimension of the airspace and the fibers are therefore important factors for fiber retention. We conclude that the sequence of wetting and immersion of inhaled and deposited MMVF 10a fibers into the aqueous lining layer by the surfactant film at the air-liquid interface is similar to that of spherical particles and is crucial for the retention of any kind of particles and fibers. Particles of identical shape, including asbestos or ceramic fibers, may have a surface free energy similar to that of vitreous fibers under ambient conditions. Presumably pre·sum·a·ble
That can be presumed or taken for granted; reasonable as a supposition: presumable causes of the disaster. , they are likewise displaced into the aqueous lining layer after their deposition in the lungs. Therefore, the increased pathogenicity of certain fibers can most likely not be explained by different retention mechanisms. Adsorption of surfactant components or proteins upon displacement into the aqueous phase by surfactant is possible and needs further investigation because it may be a crucial factor for health effects. In addition, the importance of clearance of the particulate fraction via the blood stream needs further investigation.
Table 1. Distribution of MMVF 10a in hamster lungs by TEM and shape profiles. Localization of MMVF 10a profiles Lung compartment No. (a) Percent Intrapulmonary airways 35 10.5 Free (b) 27 8.1 Phagocytosed (c) 8 2.4 Alveoli 69 20.6 Free (b) 60 17.9 Phagocytosed (c) 9 2.7 Type I cell 1 0.3 Endothelial cell 0 0 Alveolar blood capillary (d) 228 68.0 Pulmonary artery (d) 1 0.3 Interstitium 0 0 Unidentified location 1 0.3 Total 335 100 Shape profiles in TEM sections (%) Elliptical/ Partially Angular Lung compartment circular elliptical surface Intrapulmonary airways Free (b) 29.6 59.3 11.1 Phagocytosed (c) 25 50 25 Alveoli Free (b) 13.3 31.7 55.0 Phagocytosed (c) 11.1 22.2 66.7 Type I cell 0 100 0 Endothelial cell 0 0 0 Alveolar blood capillary (d) 0 11.4 68.6 Pulmonary artery (d) 0 0 100 Interstitium 0 0 0 Unidentified location 0 100 0 Total (a) Number of MMVF 10a profiles analyzed on TEM micrographs. (b) Fiber or particle profiles on lung surfaces, not within any cell. (c) Fiber or particle profiles engulfed by macrophages on lung surfaces. (d) Profiles within lumen of blood vessels.
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Marianne Geiser, (1) * Matthias Matter, (1) * Isabelle Maye, (1) Vinzenz Im Hof, (2) Peter Gehr, (1) and Samuel Schurch (3) *
(1) Institute of Anatomy and (2) Institute of Pathophysiology pathophysiology /patho·phys·i·ol·o·gy/ (-fiz?e-ol´ah-je) the physiology of disordered function.
1. , University of Bern The University of Bern is a university in the Swiss capital of Bern. It was founded in 1834. As one of the German-speaking universities in Switzerland its official name is Universität Bern, although it is frequently referred to in the French form, Université de Berne. , Bern, Switzerland; (3) Department of Physiology and Biophysics biophysics, application of various methods and principles of physical science to the study of biological problems. In physiological biophysics physical mechanisms have been used to explain such biological processes as the transmission of nerve impulses, the muscle , University of Calgary, Calgary, Alberta, Canada
Address correspondence to M. Geiser, Institute of Anatomy, Division of Histology, University of Bern, Buhlstrasse 26, CH-3000 Bern 9, Switzerland. Telephone: 41-31-631-8475. Fax: 41-31-631-3807. E-mail: firstname.lastname@example.org
* M.G., M.M., and S.S. contributed equally to this work. We thank P. Thevenaz for providing the vitreous fibers and S. Frank, B. Kupferschmid, B. Krieger, T. Weissbach, and K. Babl for excellent technical assistance.
This work was supported by Swiss National Science Foundation The Swiss National Science Foundation is a science research support organization mandated by the Swiss Federal Government. The SNSF was established in 1952 as a foundation under private law. Its secretariat is based in Berne. grant 32-65352.01, Canadian Institutes of Health Research Canadian Institutes of Health Research (CIHR) is the major federal agency responsible for funding health research in Canada. It is the successor to the Medical Research Council of Canada. , the Alberta Heritage Foundation for Medical Research, and the Silva Casa Foundation.
The authors declare they have no conflict of interest.
Received 16 July 2002; accepted 8 January 2003.