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Molecular Mechanisms of Ventilator-Induced Lung Injury.

Byline: Lin. Chen, Hai-Fa. Xia, You. Shang, Shang-Long. Yao

Objective: Mechanical ventilation (MV) has long been used as a life-sustaining approach for several decades. However, researchers realized that MV not only brings benefits to patients but also cause lung injury if used improperly, which is termed as ventilator-induced lung injury (VILI). This review aimed to discuss the pathogenesis of VILI and the underlying molecular mechanisms. Data Sources: This review was based on articles in the PubMed database up to December 2017 using the following keywords: 'ventilator-induced lung injury', 'pathogenesis', 'mechanism', and 'biotrauma'. Study Selection: Original articles and reviews pertaining to mechanisms of VILI were included and reviewed. Results: The pathogenesis of VILI was defined gradually, from traditional pathological mechanisms (barotrauma, volutrauma, and atelectrauma) to biotrauma. High airway pressure and transpulmonary pressure or cyclic opening and collapse of alveoli were thought to be the mechanisms of barotraumas, volutrauma, and atelectrauma. In the past two decades, accumulating evidence have addressed the importance of biotrauma during VILI, the molecular mechanism underlying biotrauma included but not limited to proinflammatory cytokines release, reactive oxygen species production, complement activation as well as mechanotransduction. Conclusions: Barotrauma, volutrauma, atelectrauma, and biotrauma contribute to VILI, and the molecular mechanisms are being clarified gradually. More studies are warranted to figure out how to minimize lung injury induced by MV.

Introduction

Mechanical ventilation (MV) is essential life support for patients with acute respiratory distress syndrome (ARDS); however, it can also lead to ventilator-induced lung injury (VILI) due to regional alveolar overstretch and/or repetitive alveolar collapse, which were termed as barotrauma, volutrauma, and atelectrauma. Gradually, clinicians realized that MV also mediated pulmonary injury without causing volutrauma or atelectrauma, even multi-organ dysfunction syndrome, and systemic inflammatory response. Indeed, the concept of VILI has been shifted from conventional barotraumas/volutrauma/atelectrauma to modernized biotrauma,[1],[2],[3] in which the inflammatory mediators were found to be responsible for the onset of VILI.

To understand the mechanisms of VILI are one thing, to apply MV and avoid VILI are another. Ideally, MV should maintain lung units open throughout the ventilator cycle, which minimizes lung injury due to repetitive alveolar collapse and/or overdistention. Guidelines for clinical practices are needed when it comes to how to ventilate the critical illness with or without ARDS, such as whether or not to apply low tidal volume (V[sub]T) ventilation. An integrated understanding of the molecular pathways regarding VILI is the foundation of choosing the right strategy of MV, which certainly will help clinicians to make decisions in their daily work. This review addressed several core mechanisms underlying VILI.

Molecular Mechanisms of Ventilator-Induced Lung Injury

Barotrauma

MV is an important way to provide sufficient oxygen to peripheral organs and therefore maintain their normal function. At the first beginning, it was recognized that lungs ventilated with high ventilatory pressures are prone to air leaks, which was the origin of barotrauma.[4] Actually, VILI was synonymous with barotrauma for many years. Disruption of the normal airspace wall causes the accumulation of air beyond alveoli and leads to tension pneumothorax. This particular adverse consequence is obvious and can be observed by physicians easily.

Volutrauma

Apart from the physical alveolar disruption induced by MV, researchers realized that it was excessive lung volume which leads to overdistention of the lung, i.e., volutrauma, characterized by hyperpermeability of the alveolar-capillary barrier.[5] A classical experiment found that pulmonary edema and cellular ultrastructural abnormalities were encountered only in rats subjected to high V[sub]T but not in those in which lung distention was limited by thoracoabdominal strapping, which highlighted the effect of transpulmonary pressure instead of airway pressure during VILI. The importance of transpulmonary pressure and how it can predict the risk of VILI has been discussed elsewhere.[6] Meanwhile, the direct effect of volutrauma results in a persistent cyclic stretch during MV, which stimulates alveolar epithelial and vascular endothelial cells through mechanosensitive membrane-associated protein and ion channels, finally leads to pulmonary edema.[7]

Atelectrauma

Later on, studies had shown that the repetitive opening and collapse of alveolar plays a pivotal role in VILI, which was known as atelectrauma. Atelectrauma is defined as lung injury caused by high shear forces from cyclic opening and collapse of atelectatic but recruitable lung units. As for atelectatic alveoli, local stress and strain of epithelial cells is generated during recruitment at the interface between the air bolus and collapsed airway, which causes mechanical injury. In the other scenario, such as in the alveoli filled with water, the formation and destruction of bubbles at the gas-liquid interface contributes additional local stress and causes membrane-cytoskeletal adhesions disruption and worsens lung injury.[8] One study reported that surfactant-deactivated lungs developed significant histopathology only in lung areas with unstable alveoli, which confirmed that alveolar instability is an independent cause of VILI.[9]

Biotrauma

The role of biotrauma in the pathogenesis of VILI was not clarified until 1998.[10] In certain circumstances, MV is able to initiate inflammation and lung injury while maintain gas exchange. The study of Slutsky and Tremblay[11] first suggested that the MV-induced inflammatory response may contribute to the development of multiple system organ dysfunction including respiratory failure in mechanically ventilated patients with ARDS. Since then, more attention has been paid to how MV triggers biotrauma within the lung. Accumulating evidence showed that biotrauma induced by MV is far more complicated than barotrauma, volutrauma, or atelectrauma and the underlying mechanisms can be categorized in the following four parts.

Proinflammatory mediators release

MV is able to trigger the release of numerous proinflammatory mediators that may induce lung injury and impair pulmonary function. High V[sub]T ventilation increases interleukin (IL)-1[sz], IL-6, IL-8, tumor-necrosis factor (TNF)-a, C-X-C motif ligand 1 (CXCL1) and CXCL10, macrophage inflammatory protein (MIP)-2, and intercellular cell adhesion molecule levels in the bronchoalveolar lavage fluid (BALF) in mice with a significant increase in pulmonary vascular permeability.[12],[13],[14],[15],[16] Among these, the levels of IL-6 and IL-1[sz] in the lung and BALF of IKK[sz]?mye mice were also found to cause nuclear factor-?B (NF-?B) activation in ventilator-induced IL-6 and IL-1[sz] production. A significant decrease in ventilation-induced IL-6 levels in the lung and BALF was observed in IKK[sz]?mye mice compared to WT mice while left IL-1[sz] unaffected. The decreased IL-6 levels and reduced VILI in IKK[sz]?mye mice suggested that NF-?B activation-induced IL-6 expression may contribute to VILI.[12] Intratracheal administration of IL-6 itself increased cell count and protein concentration in the BALF, while high V[sub]T MV further increased lung permeability following IL-6 administration in mice. In vitro study also showed that IL-6 increased the permeability of pulmonary endothelial cells in a Rho-independent manner.[17] One research reported that MV increased the expression of IL-8 and monocyte chemoattractant protein-1 modestly when compared with the control group; however, the increase was more evident in mice treated with both MV and lipopolysaccharide,[18] which suggested that MV is capable of augmenting the preexisting inflammatory response.

Another research showed that rats with VILI were associated with high expression of IL-33 in lung tissue; it also indicated that the membrane form of IL-33 receptor translocation from cytosol to the cell membranes of lung tissue can be seen as a new biomarker of VILI.[19] Hoegl et al .[20] demonstrated that high-pressure ventilation increased the concentrations of MIP-2 and IL-1[sz] in BALF and plasma and this increase can be reduced by inhalation of IL-10 in mice. In addition, IL-10 inhibited nitrogen oxide (NO)-release from alveolar macrophages, reduced heat shock protein-70 expression, and even reduced the activation of matrix metalloproteinase (MMP)-9 in BALF in a dose-dependent manner. In contrast to the detrimental role of TNF-a in lung injury, TNF-a derived TIP peptide is able to protect the lung against injurious ventilation. Studies had proved that TNF-a derived TIP peptide inhalation could reduce the extravascular lung water index as well as increase the PaO(2)/FiO(2) ratio.[21],[22] The protective role of TNF-derived TIP peptide lies in that through binding to epithelial sodium channel-a, it is able to strengthen the barrier function and maintain permeability of the alveolar-capillary barrier.[23]

MMPs also participate in the pathogenesis of VILI. In a lung injury model of mice induced by sepsis followed by high V[sub]T ventilation, WNT/[sz]-catenin signaling pathway was activated as the protein levels of WNT5A and [sz]-catenin increases, more MMP-7 was released in this process. Which then causes significant lung inflammation and perivascular edema.[24] The activity of MMP-9 is highly related to neutrophil transmigration during VILI and its detrimental role is evident. High V[sub]T ventilation increases acute lung injury score, neutrophil infiltration, and myeloperoxidase (MPO) activity, along with higher MMP-9 activity. However, pretreatment with MMP inhibitor mitigates VILI, as well as neutrophil infiltration and MPO activity, which suggests that inhibition of MMP-9 exert protective effect against VILI through downregulation of neutrophil-mediated inflammation.[25] Meanwhile, MMP-8 is also involved in the initiation of lung inflammation. In comparison with control group, MMP-8 deficient mice ventilated with high pressure resulted in improved gas exchange, decreased pulmonary edema, and less histopathological changes in lung tissues. Interestingly, MMP-8 deficient mice showed different immune reaction against injurious ventilation, characterized by lower levels of interferon-a and MIP-2, and increased levels of anti-inflammatory mediators (IL-4 and IL-10) as well as inhibited neutrophil infiltration. An inhibitor of MMP-8 was also shown to confer protective effect in limiting VILI.[26]

However, a study conducted by Gonzalez-Lopez et al .[27] showed different results. To a better understanding of mechanisms of repair after VILI, they set up control groups with other two different groups: (1) injury group (90 min of high-pressure ventilation without positive end-expiratory pressure [PEEP]) and (2) repair group (injury followed by 4 h of low-pressure ventilation with PEEP). Research data showed that histopathological injury and pulmonary permeability accompanied by a robust proinflammatory response during lung injury, which were reverted partially in the repair group. However, the expression of MMP-2 and MMP-9 both increased following injury and remained elevated during repair. Furthermore, MMP inhibitor doxycycline blunted lung repair after VILI and specific MMP-2 inhibition delayed lung epithelial repair in vitro . It has also been shown that administration with exogenous MMP-9 was capable of reducing lung damage and promote repair in neutropenic mice with VILI.[28] These data highlighted that MMP-2 and MMP-9 potentially promote lung epithelial repair after VILI, yet its mechanisms remain to be investigated.

Reactive oxygen species generation

Apart from proinflammatory mediators, the other potential initiating signal for biotrauma during VILI may be increased production of reactive oxygen species (ROS) in the lung triggered by cyclic stretch. Increased ROS production in response to mechanical stress has been described in various cell types. Endothelial cell production of ROS has been shown to be increased in response to shear stress as well as to cyclic mechanical stretch.[29],[30] It was reported that A549 cells subjected to cyclic stretch significantly increased levels of isoprostane (a marker of oxidant injury) with obvious decreased glutathione (GSH, an endogenous antioxidant) 60 min after cyclic stretch. Pretreatment with antioxidants prevented the elevated level of isoprostane.[31] Chapman et al .[32] showed that strain level of 10% did not increase O[sub]2− concentration in 16HBE (an immortalized human airway epithelial cell line) cells after 2 h, whereas 15%, 20%, or 30% significantly increased the generation of O[sub]2−. NADPH oxidase activity was upregulated after 2 h of cyclic mechanical stretch, which contributed to the production of O[sub]2−. Using a mitochondrial complex I inhibitor, they proved that rotenone could partially abrogate the generation of O[sub]2− induced by 2 h cyclic mechanical stretch, suggesting that increased ROS production in lung epithelia in response to elevated stretch may contribute to VILI. Recently, Tanaka et al .[33] reported that 24 h of cyclic mechanical stretch mediated a significant release of 8-isoprostane and 3-nitrotyrosine (oxidative stress markers) in A549 cells; it also increased the expression of nicotine adenine dinucleotide phosphate oxidases (NOXs). In addition, cyclic mechanical stretch-induced NOX activation was associated with late phase apoptosis/necrosis in alveolar epithelial cells.

However, the link between ROS generation induced by cyclic stretch and the loss of function of alveolar epithelial cells is still missing. To figure out the possible relationship mentioned above, Davidovich et al .[34] performed the following experiment. First, they detected the production of ROS induced by cyclic stretch in Type I-like rat alveolar epithelial cells using cell-permeant fluorogenic probe. The level of ROS and release of NO were increased after 10 min and 60 min of cyclic stretch at 37% change in surface area compared with the unstretched cells. Next, the permeability of Type I-like rat alveolar epithelial cells monolayer stimulated by ROS was assessed. In comparison to control group, cells treated with NO donor and superoxide donor showed a significant increase in the monolayer permeability. Hyperpermeability of rat alveolar epithelial cells monolayer was accompanied by NF-?B and ERK signaling pathway activation. Tight junctions (TJs) located between adjacent Type I epithelial cells are the primary barrier to paracellular transport. Song et al .[35] investigated whether ROS is able to rearrange TJs in alveolar epithelial cells and mediate barrier malfunction during cyclic stretch or not. This time, they used a precision cut lung slices model as well as rat alveolar epithelial cells under identical mechanical loads. Results indicated that in similar to rat alveolar epithelial cells under cyclic stretch, the novel model showed ROS generation under uniform and cyclic stretch. Furthermore, their permeability increased after stretch as TJs protein (occludin, claudin-4) dissociated from zona occludins-1.

Given the important role of ROS generation in the pathogenesis of VILI, researchers have been working hard to find ways to reduce ROS biosynthesis to prevent it. Recently, one study reported that apocynin (a naturally occurring methoxy-substituted catechol which inhibits NADPH oxidase in activated leukocytes) prevented VILI.[36] In detail, VILI was induced by MV with high V[sub]T utilizing isolated and perfused rat lung, an increase in lung permeability and lung weight gain can be observed in this model. The level of proinflammatory cytokines increased in BALF, concentrations of carbonyl and H[sub]2O[sub]2 were higher in BALF, mitogen-activated protein kinase signaling was also activated in high V[sub]T group. However, administration of apocynin at the onset of MV alleviated these inflammatory responses and maintained pulmonary permeability, along with decreased activation of NF-?B. In addition, researches have demonstrated that administration of N-acetylcysteine or resveratrol attenuated the inflammatory responses and oxidative damage in the same model.[37],[38]

Complement activation

The complement system is a major component of our innate immune system and is highly related with coagulation. Alveolar coagulopathy is associated with ALI/ARDS and VILI. Accumulating evidence had shown that activation of the complement system was involved in VILI.

Takahashi et al .[39] were the first to validate the link between complement C3 activation and VILI. They demonstrated that high V[sub]T induced lung injury and resulted in elevation of activities of thrombin, gelatin/collagenase, and MMPs in BALF in mice, suggesting C3 was activated following MV. Next, they applied MV to C3 deficiency mice and proved the activity of thrombin and MMPs were lowered compared with that in wild-type mice. Finally, they used humanized cobra venom factor (HCVF) to inactivate C3 in the lung during MV and data showed that pretreatment with HCVF significantly reduced C3 deposition within lung tissue, lung injury was also mitigated. There was another research showed a similar result. MV caused a tremendous increase of complement component C3a compared with the control group (1017 [+ or -] 283 ng/ml vs. 258 [+ or -] 82 ng/ml, P < 0.05) and lowered the arterial oxygen tension (193 [+ or -] 167 mmHg vs. 569 [+ or -] 26 mmHg, P < 0.05). Interestingly, it was shown that plasma level of C3a in mice following MV was inversely correlated with arterial oxygen tension ( R = −0.734; P < 0.001).[40]

Once C3 was activated, the complement cascade would be activated and finally form the terminal complement complex C5b-9. Liu et al .[41] reported that the activity of serum complement was higher along with aggravated pulmonary edema in a rat model of VILI compared with the control group. At the same time, they found the permeability of pulmonary endothelial monolayer was increased after soluble C5b-9 stimulation. Further research revealed that soluble C5b-9 caused a significant increase in rat pulmonary microvascular permeability by activating RhoA and led to higher expression of phosphorylated myosin light chain, finally resulted in stress fiber and gap formation.[41] Therefore, pulmonary endothelial barrier dysfunction mediated by complement activation may be involved in the pathogenesis of VILI.

Mechanotransduction and ion channel

Although the effects of MV in vivo and mechanical stretch in vitro are identified, the mechanisms of how cells transfer mechanical signals to biological signals remain elusive. After decades of research, it has been proved that the activity of ion channel changed quickly in response to mechanical stress and contributed to vascular hyperpermeability.[42]

Recent studies suggested the detrimental role of transient receptor potential vanilloid (TRPV) in the development of lung injury induced by MV or other insults. In particular, TRPV4 is a calcium permeable cation channel gated by various stimuli, including heat, osmotic stimuli as well as mechanical stimuli. It is expressed in a diverse range of tissues and cells, such as lung, kidney, brain, liver, and vascular endothelium.[43] In 1998, Parker et al .[44] reported that gadolinium (which is able to block stretch-activated nonselective cation channels) inhibited the increase in vascular permeability induced by high airway pressure ventilation in isolated rat lung, demonstrating that stretch-activated cation channels could trigger acute vascular hyperpermeability after MV. Moreover, Hamanaka et al .[45] clarified the specific role of TRPV4 during VILI in 2007. First, they applied high peak inflation pressure (PIP) to isolated perfused lungs and evaluated the permeability as indexed by filtration coefficient (K[sub]f). Research showed high PIP ventilation increased pulmonary permeability compared with baseline but pretreatment with TRPV4 inhibitor abolished this effect. In isolated perfused lungs from TRPV4 knockout mice, the same ventilation setting failed to increase K[sub]f. Next, they demonstrated lung distention mediated by ventilation caused Ca2+ entry in the control group, alveolar and perivascular edema were also induced. However, high PIP ventilation-induced Ca2+ entry and perivascular edema were abrogated in TRPV4-/- lungs.[46] Interestingly, they conducted another research and proved that high PIP ventilation induced calcium entry, NO and O[sub]2- production through activating TRPV4 macrophages, which was the reason why vascular permeability in lung increased rapidly following high pressure ventilation.[46]

It was reported that TRPV4 and its upstream kinase-mediated lung injury after high V[sub]T MV.[47] By utilizing real-time imaging of endothelial Ca2+ in intact lungs, Michalick et al .[47] were able to show that acute airway pressure elevation in normal mice caused an evident increase in endothelial Ca2+ and lasted for more than 15 min, whereas TRPV4 inhibitor abolished the increase. TRPV4 has also been found to be a key mediator during inflammatory cell infiltration, inflammatory cytokines, and chemokines release as well as edema formation in mice ventilated with high V[sub]T. In addition, as serum glucocorticoid regulated kinase 1 (SGK1) inhibition mitigated TRPV4-mediated endothelial Ca2+ entry, proinflammatory cytokines release, and prevented Ser824 phosphorylation of TRPV4 induced by mechanical stretch, the authors revealed that both SGK1 (an upstream regulator of TRPV4) and TRPV4 were critical molecules in VILI. Given the role of TRPV4 in VILI, numerous researches had demonstrated that inhibition of TRPV4 by knockout or its pharmacological inhibitor confer lung protection, including attenuated inflammation and improved pulmonary function, against VILI or ALI induced by chemical reagents.[47],[48]

As stretch-activated two-pore domain K+ channel (K2P) TREK-1 participated in the regulation of inflammation response and repair, whether it can regulate the mechanobiology of alveolar epithelial cells or not has been investigated. TREK-1 deficient A549 cells showed less F-actin formation while its deformability increased, which also induced higher expression of phosphorylated FAK. Thus, alveolar epithelial cells expressed TREK-1 were more sensitive to stretch-induced lung injury.[49],[50]

Different from the effect of TREK-1, Na+ transport by Na+-K+-ATPase facilitated the clearance of pulmonary edema.[51],[52],[53],[54],[55],[56] One study demonstrated that 30 min or 60 min of cyclic stretch-induced an increase of Na+-K+-ATPase in murine lung epithelial cells.[51] Fisher and Margulies[52] reported that in Type II alveolar epithelial cells, the activity of Na+-K+-ATPase was increased in response to cyclic stretch in a dose-dependent manner while lasting tonic stretch showed no effect on Na+ pump. Furthermore, Fisher and Margulies[53] set up a new model which could evaluate the relationship between plasma membrane tension and Na+-K+-ATPase stimulation. They proved that MV with PEEP (with constant amplitude and relatively high volume) was associated with highest Na+-K+-ATPase stimulation. Interestingly, a recent study revealed that [sz]1 subunit of Na+-K+-ATPase played a vital role in alveolar fluid clearance during VILI.[54]

Conclusions

In summary, inappropriate use of MV will lead to VILI and a better understanding of biotrauma is required. Biotrauma is characterized partially by proinflammatory responses within the lung or in the circulatory system, which can explain the lung-organ crosstalk and interactions (including MODS). From traditional concept 'barotraumas, volutrauma, and atelectrauma' to a relatively newly recognized biotrauma, the mechanisms underlying VILI is still developing. There is an intrinsic relationship between the traditional mechanisms and biotrauma. Traditional ones are established on the basis of lung structure and function, which can be observed easily. However, biotrauma emphasis on signal transduction and direct effect of mechanical stress within cells. For example, high V[sub]T ventilation is able to cause lung injury, this can be seen as volutrauma; it also can be explained by biotrauma, alveolar epithelium sense, and transform mechanical stress to biological signal, which then increase the activity of TRPV4 and result in hyperpermeability and edema. Based on these, many factors should be considered when providing MV to a critically ill patient. Lung protective strategies should be applied depend on individualized situation to improve the outcomes of ARDS patients.

Financial support and sponsorship

This study was supported by grants from the National Natural Science Foundation of China (No. 81372036, No. 81671890, No. 81601669, and No. 81500064).

Conflicts of interest

There are no conflicts of interest.

References

1. Curley GF, Laffey JG, Zhang H, Slutsky AS. Biotrauma and ventilator-induced lung Injury: Clinical implications. Chest 2016;150:1109-17. doi: 10.1016/j.chest.2016.07.019.

2. Slutsky AS, Ranieri VM. Ventilator-induced lung injury. N Engl J Med 2013;369:2126-36. doi: 10.1056/NEJMra1208707.

3. Wang ZY, Li T, Wang CT, Xu L, Gao XJ. Assessment of 1-year outcomes in survivors of severe acute respiratory distress syndrome receiving extracorporeal membrane oxygenation or mechanical ventilation: A Prospective observational study. Chin Med J 2017;130:1161-8. doi: 10.4103/0366-6999.205847.

4. Gajic O, Dara SI, Mendez JL, Adesanya AO, Festic E, Caples SM, et al . Ventilator-associated lung injury in patients without acute lung injury at the onset of mechanical ventilation. Crit Care Med 2004;32:1817-24. doi: 10.1097/01.CCM.0000133019.52531.30

5. Pan C, Chen L, Zhang YH, Liu W, Urbino R, Ranieri VM, et al. Physiological correlation of airway pressure and transpulmonary pressure stress index on respiratory mechanics in acute respiratory failure. Chin Med J 2016;129:1652-7. doi: 10.4103/0366-6999.185855.

6. Grieco DL, Chen L, Brochard L. Transpulmonary pressure: Importance and limits. Ann Transl Med 2017;5:285. doi: 10.21307/atm.2017.07.22.

7. Lionetti V, Recchia FA, Ranieri VM. Overview of ventilator-induced lung injury mechanisms. Curr Opin Crit Care 2005;11:82-6.

8. Bilek AM, Dee KC, Gaver DP 3rd. Mechanisms of surface-tension-induced epithelial cell damage in a model of pulmonary airway reopening. J Appl Physiol (1985) 2003;94:770-83. doi: 10.1152/japplphysiol.00764.2002.

9. Steinberg JM, Schiller HJ, Halter JM, Gatto LA, Lee HM, Pavone LA, et al. Alveolar instability causes early ventilator-induced lung injury independent of neutrophils. Am J Respir Crit Care Med 2004;169:57-63. doi: 10.1164/rccm.200304-544OC.

10. Tremblay LN, Slutsky AS. Ventilator-induced injury: From barotrauma to biotrauma. Proc Assoc Am Physicians 1998;110:482-8.

11. Slutsky AS, Tremblay LN. Multiple system organ failure. Is mechanical ventilation a contributing factor? Am J Respir Crit Care Med 1998;157:1721-5. doi: 10.1164/ajrccm.157.6.9709092.

12. Ko YA, Yang MC, Huang HT, Hsu CM, Chen LW. NF-?B activation in myeloid cells mediates ventilator-induced lung injury. Respir Res 2013;14:69. doi: 10.1186/1465-9921-14-69.

13. Kuipers MT, Vogl T, Aslami H, Jongsma G, van den Berg E, Vlaar AP, et al. High levels of S100A8/A9 proteins aggravate ventilator-induced lung injury via TLR4 signaling. PLoS One 2013;8:e68694. doi: 10.1371/journal.pone.0068694.

14. Nickles HT, Sumkauskaite M, Wang X, Wegner I, Puderbach M, Kuebler WM, et al. Mechanical ventilation causes airway distension with proinflammatory sequelae in mice. Am J Physiol Lung Cell Mol Physiol 2014;307:L27-37. doi: 10.1152/ajplung.00288.2013.

15. Lex D, Uhlig S. One-hit models of ventilator-induced lung injury: Benign inflammation versus inflammation as a by-product. Anesthesiology 2017;126:909-22. doi: 10.1097/ALN.0000000000001605.

16. Wang X, Zhang R, Tong Y, Ding X, Jin S, Zhao X, et al. High-mobility group box1 protein is involved in the protective effect of saquinavir on ventilation-induced lung injury in mice. Acta Biochim Biophys Sin (Shanghai) 2017;49:907-15. doi: 10.1093/abbs/gmx085.

17. Birukova AA, Tian Y, Meliton A, Leff A, Wu T, Birukov KG, et al. Stimulation of rho signaling by pathologic mechanical stretch is a 'second hit' to rho-independent lung injury induced by IL-6. Am J Physiol Lung Cell Mol Physiol 2012;302:L965-75. doi: 10.1152/ajplung.00292.2011.

18. Altemeier WA, Matute-Bello G, Frevert CW, Kawata Y, Kajikawa O, Martin TR, et al. Mechanical ventilation with moderate tidal volumes synergistically increases lung cytokine response to systemic endotoxin. Am J Physiol Lung Cell Mol Physiol 2004;287:L533-42. doi: 10.1152/ajplung.00004.2004.

19. Yang SH, Lin JC, Wu SY, Huang KL, Jung F, Ma MC, et al. Membrane translocation of IL-33 receptor in ventilator induced lung injury. PLoS One 2015;10:e0121391. doi: 10.1371/journal.pone.0121391.

20. Hoegl S, Boost KA, Czerwonka H, Dolfen A, Scheiermann P, Muhl H, et al. Inhaled IL-10 reduces biotrauma and mortality in a model of ventilator-induced lung injury. Respir Med 2009;103:463-70. doi: 10.1016/j.rmed.2008.09.020.

21. Hartmann EK, Boehme S, Duenges B, Bentley A, Klein KU, Kwiecien R, et al. An inhaled tumor necrosis factor-alpha-derived TIP peptide improves the pulmonary function in experimental lung injury. Acta Anaesthesiol Scand 2013;57:334-41. doi: 10.1111/aas.12034.

22. Hartmann EK, Thomas R, Liu T, Stefaniak J, Ziebart A, Duenges B, et al. TIP peptide inhalation in experimental acute lung injury: Effect of repetitive dosage and different synthetic variants. BMC Anesthesiol 2014;14:42. doi: 10.1186/1471-2253-14-42.

23. Czikora I, Alli AA, Sridhar S, Matthay MA, Pillich H, Hudel M, et al. Epithelial sodium channel-a mediates the protective effect of the TNF-derived TIP peptide in pneumolysin-induced endothelial barrier dysfunction. Front Immunol 2017;8:842. doi: 10.3389/fimmu.2017.00842.

24. Villar J, Cabrera NE, Casula M, Valladares F, Flores C, Lopez-Aguilar J, et al. WNT/[sz]-catenin signaling is modulated by mechanical ventilation in an experimental model of acute lung injury. Intensive Care Med 2011;37:1201-9. doi: 10.1007/s00134-011-2234-0.

25. Kim JH, Suk MH, Yoon DW, Lee SH, Hur GY, Jung KH, et al. Inhibition of matrix metalloproteinase-9 prevents neutrophilic inflammation in ventilator-induced lung injury. Am J Physiol Lung Cell Mol Physiol 2006;291:L580-7. doi: 10.1152/ajplung.00270.2005.

26. Albaiceta GM, Gutierrez-Fernandez A, Garcia-Prieto E, Puente XS, Parra D, Astudillo A, et al. Absence or inhibition of matrix metalloproteinase-8 decreases ventilator-induced lung injury. Am J Respir Cell Mol Biol 2010;43:555-63. doi: 10.1165/rcmb.2009-0034OC.

27. Gonzalez-Lopez A, Astudillo A, Garcia-Prieto E, Fernandez-Garcia MS, Lopez-Vazquez A, Batalla-Solis E, et al. Inflammation and matrix remodeling during repair of ventilator-induced lung injury. Am J Physiol Lung Cell Mol Physiol 2011;301:L500-9. doi: 10.1152/ajplung.00010.2011.

28. Blazquez-Prieto J, Lopez-Alonso I, Amado-Rodriguez L, Huidobro C, Gonzalez-Lopez A, Kuebler WM, et al. Impaired lung repair during neutropenia can be reverted by matrix metalloproteinase-9. Thorax 2017. pii: thoraxjnl-2017-210105. doi: 10.1136/thoraxjnl-2017-210105.

29. Parinandi NL, Kleinberg MA, Usatyuk PV, Cummings RJ, Pennathur A, Cardounel AJ, et al. Hyperoxia-induced NAD(P)H oxidase activation and regulation by MAP kinases in human lung endothelial cells. Am J Physiol Lung Cell Mol Physiol 2003;284:L26-38. doi: 10.1152/ajplung.00123.2002.

30. Ali MH, Pearlstein DP, Mathieu CE, Schumacker PT. Mitochondrial requirement for endothelial responses to cyclic strain: Implications for mechanotransduction. Am J Physiol Lung Cell Mol Physiol 2004;287:L486-96. doi: 10.1152/ajplung.00389.2003.

31. Jafari B, Ouyang B, Li LF, Hales CA, Quinn DA. Intracellular glutathione in stretch-induced cytokine release from alveolar type-2 like cells. Respirology 2004;9:43-53. doi: 10.1111/j.1440-1843.2003.00527.x.

32. Chapman KE, Sinclair SE, Zhuang D, Hassid A, Desai LP, Waters CM, et al. Cyclic mechanical strain increases reactive oxygen species production in pulmonary epithelial cells. Am J Physiol Lung Cell Mol Physiol 2005;289:L834-41. doi: 10.1152/ajplung.00069.2005.

33. Tanaka T, Saito Y, Matsuda K, Kamio K, Abe S, Kubota K, et al. Cyclic mechanical stretch-induced oxidative stress occurs via a NOX-dependent mechanism in type II alveolar epithelial cells. Respir Physiol Neurobiol 2017;242:108-16. doi: 10.1016/j.resp.2017.04.007.

34. Davidovich N, DiPaolo BC, Lawrence GG, Chhour P, Yehya N, Margulies SS, et al. Cyclic stretch-induced oxidative stress increases pulmonary alveolar epithelial permeability. Am J Respir Cell Mol Biol 2013;49:156-64. doi: 10.1165/rcmb.2012-0252OC.

35. Song MJ, Davidovich N, Lawrence GG, Margulies SS. Superoxide mediates tight junction complex dissociation in cyclically stretched lung slices. J Biomech 2016;49:1330-5. doi: 10.1016/j.jbiomech.2015.10.032.

36. Chiang CH, Chuang CH, Liu SL, Lee TS, Kou YR, Zhang H, et al. Apocynin attenuates ventilator-induced lung injury in an isolated and perfused rat lung model. Intensive Care Med 2011;37:1360-7. doi: 10.1007/s00134-011-2251-z.

37. Chiang CH, Chuang CH, Liu SL, Chian CF, Zhang H, Ryu JH, et al. N-acetylcysteine attenuates ventilator-induced lung injury in an isolated and perfused rat lung model. Injury 2012;43:1257-63. doi: 10.1016/j.injury.2011.12.026.

38. Dong WW, Liu YJ, Lv Z, Mao YF, Wang YW, Zhu XY, et al. Lung endothelial barrier protection by resveratrol involves inhibition of HMGB1 release and HMGB1-induced mitochondrial oxidative damage via an Nrf2-dependent mechanism. Free Radic Biol Med 2015;88:404-16. doi: 10.1016/j.freeradbiomed.2015.05.004.

39. Takahashi K, Saha D, Shattino I, Pavlov VI, Stahl GL, Finnegan P, et al. Complement 3 is involved with ventilator-induced lung injury. Int Immunopharmacol 2011;11:2138-43. doi: 10.1016/j.intimp.2011.09.008.

40. Petersen B, Busch T, Gaertner J, Haitsma JJ, Krabbendam S, Ebsen M, et al . Complement activation contributes to ventilator-induced lung injury in rats. J Physiol Pharmacol 2016;67:911-8.

41. Liu K, Mao YF, Zheng J, Peng ZY, Liu WW, Liu Y, et al. SC5b-9-induced pulmonary microvascular endothelial hyperpermeability participates in ventilator-induced lung injury. Cell Biochem Biophys 2013;67:1421-31. doi: 10.1007/s12013-013-9675-8.

42. Schwingshackl A. The role of stretch-activated ion channels in acute respiratory distress syndrome: Finally a new target? Am J Physiol Lung Cell Mol Physiol 2016;311:L639-52. doi: 10.1152/ajplung.00458.2015.

43. Vriens J, Watanabe H, Janssens A, Droogmans G, Voets T, Nilius B, et al. Cell swelling, heat, and chemical agonists use distinct pathways for the activation of the cation channel TRPV4. Proc Natl Acad Sci U S A 2004;101:396-401. doi: 10.1073/pnas.0303329101.

44. Parker JC, Ivey CL, Tucker JA. Gadolinium prevents high airway pressure-induced permeability increases in isolated rat lungs. J Appl Physiol (1985) 1998;84:1113-8. doi: 10.1152/jappl.1998.84.4.1113.

45. Hamanaka K, Jian MY, Weber DS, Alvarez DF, Townsley MI, Al-Mehdi AB, et al. TRPV4 initiates the acute calcium-dependent permeability increase during ventilator-induced lung injury in isolated mouse lungs. Am J Physiol Lung Cell Mol Physiol 2007;293:L923-32. doi: 10.1152/ajplung.00221.2007.

46. Hamanaka K, Jian MY, Townsley MI, King JA, Liedtke W, Weber DS, et al. TRPV4 channels augment macrophage activation and ventilator-induced lung injury. Am J Physiol Lung Cell Mol Physiol 2010;299:L353-62. doi: 10.1152/ajplung.00315.2009.

47. Michalick L, Erfinanda L, Weichelt U, van der Giet M, Liedtke W, Kuebler WM, et al. Transient receptor potential vanilloid 4 and serum glucocorticoid-regulated kinase 1 are critical mediators of lung injury in overventilated mice in vivo . Anesthesiology 2017;126:300-11. doi: 10.1097/ALN.0000000000001443.

48. Balakrishna S, Song W, Achanta S, Doran SF, Liu B, Kaelberer MM, et al. TRPV4 inhibition counteracts edema and inflammation and improves pulmonary function and oxygen saturation in chemically induced acute lung injury. Am J Physiol Lung Cell Mol Physiol 2014;307:L158-72. doi: 10.1152/ajplung.00065.2014.

49. Roan E, Waters CM, Teng B, Ghosh M, Schwingshackl A. The 2-pore domain potassium channel TREK-1 regulates stretch-induced detachment of alveolar epithelial cells. PLoS One 2014;9:e89429. doi: 10.1371/journal.pone.0089429.

50. Schwingshackl A, Teng B, Makena P, Ghosh M, Sinclair SE, Luellen C, et al . Deficiency of the two-pore-domain potassium channel TREK-1 promotes hyperoxia-induced lung injury. Crit Care Med 2014;42:e692-701. doi: 10.1097/CCM.0000000000000603.

51. Waters CM, Ridge KM, Sunio G, Venetsanou K, Sznajder JI. Mechanical stretching of alveolar epithelial cells increases Na(+)-K(+)-ATPase activity. J Appl Physiol (1985) 1999;87:715-21. doi: 10.1152/jappl.1999.87.2.715.

52. Fisher JL, Margulies SS. Na(+)-K(+)-ATPase activity in alveolar epithelial cells increases with cyclic stretch. Am J Physiol Lung Cell Mol Physiol 2002;283:L737-46. doi: 10.1152/ajplung.00030.2001.

53. Fisher JL, Margulies SS. Modeling the effect of stretch and plasma membrane tension on Na+-K+-ATPase activity in alveolar epithelial cells. Am J Physiol Lung Cell Mol Physiol 2007;292:L40-53. doi: 10.1152/ajplung.00425.2005.

54. Flodby P, Kim YH, Beard LL, Gao D, Ji Y, Kage H, et al. Knockout mice reveal a major role for alveolar epithelial type I cells in alveolar fluid clearance. Am J Respir Cell Mol Biol 2016;55:395-406. doi: 10.1165/rcmb.2016-0005OC.

55. Lin X, Barravecchia M, Kothari P, Young JL, Dean DA. [sz]1-Na(+), K(+)-ATPase gene therapy upregulates tight junctions to rescue lipopolysaccharide-induced acute lung injury. Gene Ther 2016;23:489-99. doi: 10.1038/gt.2016.19. Epub 2016 Mar 17.

56. Zhang JL, Zhuo XJ, Lin J, Luo LC, Ying WY, Xie X, et al . Maresin1 stimulates alveolar fluid clearance through the alveolar epithelial sodium channel Na, K-ATPase via the ALX/PI3K/Nedd4-2 pathway. Lab Invest 2017;97:543-554. doi: 10.1038/labinvest.2016.150.
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Title Annotation:Review Article
Author:Chen, Lin; Xia, Hai-Fa; Shang, You; Yao, Shang-Long
Publication:Chinese Medical Journal
Article Type:Report
Date:Oct 1, 2018
Words:5890
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