A comparison of C3a and C5a-mediated stable adhesion of rolling eosinophils in postcapillary venules and transendothelial migration in vitro and in vivo

The comparative ability of the complement anaphylatoxins C3a and C5a to med iate leukocyte adhesion and transendothelial migration in vivo and in vitro was investigated. Superfusion of IL-1 beta-stimulated rabbit mesentery wit h C3a resulted in a rapid and stable adhesion of rolling eosinophils, but n ot neutrophils, to postcapillary venules, However, C3a failed to evoke subs equent transmigration of the adherent eosinophils. In contrast, C5a induced both the rapid activation-dependent firm adhesion and transmigration of eo sinophils and neutrophils through venular endothelium. C3a induced selectiv e shedding of L-selectin and an increase in alpha(M)beta(2) integrin expres sion on eosinophils but not neutrophils, while C5a induced shedding of L-se lectin and upregulation of alpha(M)beta(2) integrin on both eosinophils and neutrophils, Both C3a- and C5a-dependent adhesion to venular endothelium w as blocked by ex vivo treatment of eosinophils with anti-alpha(4) and anti- beta(2) integrin mAbs. In vitro, both C3a (but not C3a(desArg)) and C5a (in cluding C5a(desArg))-dependent transmigration of eosinophils across IL-1 be ta-stimulated endothelial monolayer was mediated by alpha(4)beta(1) and alp ha(M)beta(2) integrins, Overall these studies suggest that C3a is eosinophi l-specific chemotactic mediator that influences selectively eosinophil adhe sion but not transmigration in vivo. C5a in contrast is a complete activato r of integrin-dependent adhesion as well as transmigration of eosinophils a nd neutrophils.