ROLE OF CD18 IN THE ACCUMULATION OF EOSINOPHILS AND NEUTROPHILS AND LOCAL EDEMA FORMATION IN INFLAMMATORY REACTIONS IN GUINEA-PIG SKIN

Intradermal injection of the complement fragment C5a des Arg induces l ocal oedema formation that, in rabbits and man, is dependent on circul ating neutrophils. Monoclonal antibodies to the leukocyte adhesion mol ecule CD11/CD18 Mock neutrophil accumulation and prevent neutrophil-de pendent oedema formation. The role of CD11/CD18 in mediating eosinophi l accumulation in vivo is less established. In this study we have used an anti-human CD18 monoclonal antibody, 6.5E, to investigate the neut rophil-dependency of oedema formation induced by C5a des Arg in guinea -pig skin. We also studied the role of CD18 in mediating eosinophil ac cumulation in the same model. 2 Stimulated adhesion of In-111-labelled guinea-pig neutrophils and eosinophils to serum-coated plastic was in hibited in a dose-dependent manner by 6.5E suggesting that the monoclo nal antibody recognizes and blocks the guinea-pig CD18 adhesion molecu le. 3 The accumulation of In-111-labelled neutrophils induced by zymos an-activated plasma (ZAP, as a source of C5a des Arg) in skin sites wa s reduced by up to 89% in animals treated intravenously with F(ab')(2) fragments of 6.5E. ZAP-induced accumulation of In-111-labelled eosino phils was also greatly reduced (by up to 78%) by treatment with 6.5E. 4 Despite the inhibition of ZAP-induced neutrophil accumulation by 6.5 E, local oedema formation in the same skin sites was unaffected, excep t at the top dose of ZAP, by treatment with the anti-CD18 monoclonal a ntibody, suggesting that the oedema response was largely neutrophil-in dependent. Indeed, ZAP-induced oedema formation was reduced by up to 8 1% by the H-1 receptor antagonist, mepyramine. 5 Accumulation of In-11 1-labelled eosinophils in a passive cutaneous anaphylactic (PCA) react ion was also blocked by treatment with 6.5E, while oedema formation in the same skin sites was unaffected. Intradermal injection of cationic protein-containing extracts of Schistosoma mansoni larvae also induce d the accumulation of In-111-labelled neutrophils and eosinophils whic h was abrogated by intravenous 6.5E. In contrast, extract-induced loca l oedema formation was similar in control and 6.5E-treated guinea-pigs . 6 In summary, the local accumulation of radiolabelled neutrophils at sites of inflammation in guineapig skin was dependent on the adhesion molecule CD18 while, in contrast, there was no evidence for neutrophi l-dependent oedema formation in this species. Accumulation of radiolab elled eosinophils was also dependent on CD18.