Allergy-triggering receptor made en masse.

Allergy-triggering receptor made en masse

Scientists this week reported coaxing culture monkey cells to sprout millions of the cell-surface receptors that serve as docking sites for the immune protein triggering allergic reactions in humans. The successful mass production of the so-called IgE receptor on living cells gives researchers their first chance to experiment with rationally designed molecules that can block those receptors. Such experiments may lead to the development of drugs that singlehandedly could prevent the entire gamut of allergic reactions, say the researchers and others.

In humans, two types of cells have IgE receptors -- basophils, which circulate in the blood, and mast cells, which reside in tissues such as the lungs and skin. But these cell types are rare and difficult to purify, slowing research on IgE-blocking drugs for the one out fo six people in the United States who suffer from allergies. Rather than blocking IgE binding, today's drugs interfere with the later stages of an IgE-triggered biochemical cascade that leads to sneezing, itching and the life-threatening reaction called anaphylaxis. They do so with only partial success and often cause a variety of side effects such as drowsiness or insomnia.

Jean Pierre Kinet and his colleagues at the National Institutes of Health in Bethesda, Md., performed the latest experiments in cultured monkey kidney cells -- a line of cells that can be genetically manipulated with relative ease. They used a gene-altered virus to inject into these cells pieces of DNA coding for the production of a critical portion of the human IgE receptor. They also injected genes coding for the remaining two portions of the three-component receptors, but used rat genes because no one has yet cloned the human genes for these two portions.

Once fed the three genes, the monkey cells made millions of human-rat receptors that bound human IgE just as normal human IgE receptors do, report Kinet, Larry Miller, Henry Metzger and Ulrich Blank in the April 21 SCIENCE.

"I'd say this is one of the holy grails of immunology of allergy -- to understand the hook by which IgE attaches to cells," says Philip Askenase, an allergy researcher at Yale University in New Haven, Conn. He says scientists have yet to characterize many other immune system receptors. "But from the point of view of human disease, this is the one. IgE allergies are tremendously important and common diseases."

Kinet says his team has partially succeeded in expressing the IgE receptor in a more stable line of cells taken from hamster ovaries, and is "very close" to cloning the human versions of the remaining two subunits of the receptor. The researchers are collaborating with Hoffmann-La Roche Inc., a pharmaceutical company based in Nutley, N.J.

Kinet and others say that IgE, mast cells and basophils probably play some useful, but perhaps not critical, roles in the body. Mast-cell-deficient mice suffer no apparent signs of immunological deficiency.

Says Kinet: "Maybe these cells are involved in some immunological defense, but maybe not so critically that if you inhibited that receptor you'd have any real problem."