Signaling through the beta 2 integrin prolongs eosinophil survival

Background: Recently, adhesion molecules have been suggested to play an imp ortant role in allergic inflammatory diseases such as bronchial asthma. It is unclear whether eosinophil activation and paracrine or autocrine synthes is of eosinophilopoietic growth cytokines is mediated through signaling by intercellular adhesion molecule-1 (ICAM-1) and the beta 2 integrin family. Objective: We examined whether signaling by ICAM-1 and its ligands (beta 2 integrins) could prolong eosinophil survival. Methods: Eosinophils were isolated from patients with hypereosinophilia by modified CD16 negative selection. After culture with or without recombinant soluble ICAM-1, eosinophil viability was measured by trypan blue dye exclu sion. Results: Eosinophil survival was prolonged in cultures with recombinant sol uble ICAM-1 compared with cultures without it (P < .01 on days 2, 4, and 6) ; this effect was dose-dependent, Eosinophil survival in cultures with reco mbinant soluble ICAM-1 was significantly inhibited by antibodies against IC AM-1 (P < .01), complement receptor 3 (P < .01), and lymphocyte function-as sociated antigen-1 beta (P < .01), Anti-IL-3 showed no effect on eosinophil survival, whereas anti-IL-5 caused partial inhibition of survival. Interes tingly, anti-granulocyte/macrophage colony-stimulating factor caused the co mplete inhibition of eosinophil survival in cultures with recombinant solub le ICAM-1. Conclusion: These results suggested the importance of the beta 2 integrins in eosinophil-mediated allergic inflammation.