EOSINOPHIL TRANSENDOTHELIAL MIGRATION INDUCED BY CYTOKINES .3. EFFECTOF THE CHEMOKINE RANTES

Selective eosinophil recruitment occurs after experimental Ag challeng e and in tissue sites of allergic diseases. The mechanisms of selectiv e eosinophil migration are still unknown. In our study, we examined th e ability of chemokines to induce transendothelial migration (TEM) of eosinophils in vitro. Among the chemokines tested, only RANTES induced eosinophil TEM. RANTES failed to induce TEM of neutrophils. Interesti ngly, IL-8 induced neutrophil TEM and had no effect on eosinophil TEM. RANTES-induced TEM was concentration-dependent and was inhibited by A bs directed against the beta 2 integrin CD18. When IL-1-activated endo thelial cells were utilized, RANTES-induced TEM also involved the eosi nophil beta 1 integrin VLA-4. RANTES did not increase eosinophil adhes ion to either resting or IL-1-activated endothelial cells, nor did the chemokine increase CD11b or decrease L-selectin expression. A gradien t of RANTES appears to be required for eosinophil TEM. Pre-exposure of eosinophils to IL-5 dramatically potentiated the TEM response to RANT ES. These findings suggest that the chemokine RANTES is a potent and s elective inducer of eosinophil TEM. Because RANTES appears to be produ ced in vivo during allergic reactions or in allergic diseases, we spec ulate that these findings may have some direct relevance to the mechan ism of selective eosinophil recruitment in vivo in humans.