THE ROLE OF CD11 CD18 INTEGRINS IN THE REVERSE PASSIVE ARTHUS REACTION IN RAT DERMAL TISSUE/

The CD11/CD18 leukocyte integrins are necessary for tissue localizatio n of neutrophils, an early requisite event in inflammation, We have an alyzed the contribution of CD11a/CD18 and CD11b/CD18 to local neutroph il accumulation and tissue injury in the reverse passive Arthus reacti on in the rat dermis, Experimental groups comprised animals that recei ved an intravenous infusion of (1) recombinant neutrophil inhibitory f actor (NIF), a hookworm-derived antagonist of CD11b/CD18; (2) monoclon al antibody to CD11a/CD18 (TA-3); (3) a combination of these agents; ( 4) a monoclonal antibody to CD18 (WT.3); or (5) saline. Administration of recombinant NIF or anti-CD11a/CD18 monoclonal antibody alone produ ced a slight reduction in neutrophil accumulation but did not affect e dema formation, In contrast, a combination of these antagonists yielde d a significant reduction in neutrophil accumulation and a modest redu ction in edema, equivalent to levels observed with either anti-CD18 an tibodies or animals that were rendered neutropenic, These results indi cate that neutrophil infiltration in rat dermal tissue in the reverse passive Arthus reaction is dependent predominantly on the leukocyte in tegrins CD11a/CD18 and CD11b/CD18 and that either of these integrins i s sufficient for neutrophil trafficking in this inflammatory setting.