Normally, mast cells respond with an outpouring of histamine, prostaglandins and other substances that spur allergic reactions in other cells. However, Bochner and his colleagues found that cells with activated Siglec-8 released less than half the typical amount of these substances.
Extending their experiment from cells to whole tissues, Bochner and his colleagues used antibodies to activate mast cells Siglec-8 in small pieces of human lung saved from autopsies. When the researchers triggered the cells to release their payloads-an act that typically causes airways to sharply constrict-the contractions were about 25 percent weaker than in lung tissue where the mast cells Siglec-8 wasnt activated.
The researchers are still unsure exactly how Siglec-8 inhibits mast cells from releasing their immune-triggering chemicals. However, follow-up experiments suggested that activating the protein keeps calcium from moving efficiently into the cells. Mast cells need this calcium signal to release their contents.
Bochner notes that researchers might eventually use these results, published in the February Journal of Allergy and Clinical Immunology, to develop a drug with this same effect. Such a drug would have the dual effect of blocking or reducing allergic reactions by killing eosinophils and preventing mast cells from releasing their substances.
Both of these effects could make allergic diseases and asthma less severe, he says. Its an intriguing approach because there are no drugs that specifically target both these cell types.
Though drugs exist that affect either eosinophils or mast cells, Bochner says developing a single drug that takes aim at both types of cells could be ev
|Contact: Christen Brownlee|
Johns Hopkins Medical Institutions