Monoclonal antibodies to leukocyte integrins CD11a/CD18 and CD11b/CD18 or intercellular adhesion molecule-1 inhibit chemoattractant-stimulated neutrophil transendothelial migration in vitro

Intercellular adhesion molecule-1 (ICAM-1) is present on the endothelium and binds to one or more members of the CD11/CD18 family of leukocyte surface integrins. To assess the role of these molecules in mediating chemotaxis of neutrophils across the endothelium, an in vitro model consisting of monolayers of human umbilical vein endothelial cells (HUVEC) grown on amniotic connective tissue was used. Neutrophils placed on the apical sides of these cultures migrated across the endothelium in response to chemoattractants added basally. Monoclonal antibodies (MoAbs) to CD11a, CD11b, and CD18 on the neutrophils inhibited this migration by 52% +/- 11%, 29% +/- 19%, and 90% +/- 7%, respectively. An MoAb to ICAM-1 inhibited transendothelial chemotaxis of the leukocytes by 55% +/- 16%. Inhibition was mediated by binding of the MoAb to ICAM-1 on the HUVEC, rather than by any direct effect of the antibody on the neutrophils. When used in combination, MoAbs to CD11a and to CD11b inhibited migration in a nearly additive fashion. A similar additive effect was observed when MoAbs to CD11b and to ICAM-1 were used together. In contrast, MoAbs to CD11a and to ICAM-1 produced no more inhibition when used in combination than when added singly. These results show that ICAM-1, CD11a/CD18, and CD11b/CD18 all participate in controlling migration of neutrophils across endothelial monolayers in response to chemotactic agents.