Monoclonal Antibodies to the Leukocyte Membrane CD18 Glycoprotein Complex and to Intercellular Adhesion Molecule-1 Inhibit Leukocyte-Endothelial Adhesion in Rabbits
Increasing evidence indicates that leukocyte-endothelium adhesion is mediated, in part, by the CD11/CD18 family of heterodimeric glycoproteins expressed on the leukocyte plasma membrane and by intercellular adhesion molecule-1 (ICAM-1) which is expressed on endothelial cells. We have used the technique of intravital microscopy to visualize the microcirculation of the rabbit mesentery and to evaluate effects of antibodies against several adhesion glycoproteins on C5a-induced leukocyte adhesion. Addition of zymosan-activated serum (a source of C5a) to the buffer superfusing the mesenteric microvasculature induced rapid adhesion of leukocytes to the endothelium of post-capillary venules. Monoclonal antibodies R15.7 (anti-CD18), R7.1 (anti-CD11a, LFA-1), and R6.5 (anti-ICAM-1), administered intravenously before C5a exposure, strongly inhibited leukocyte adherence while antibody LM2 (anti-CD11b, Mac-1) produced significant, but weaker, inhibition. If these antibodies were administered after C5a-induced adhesion had begun, both R15.7 and R7.1 displaced adherent leukocytes and prevented further leukocyte accumulation: LM2 and R6.5 did not displace adherent leukocytes or inhibit incoming leukocytes from adhering. These data confirm earlier findings establishing a role for CD18 in leukocyte adhesion in vivo and extend those observations to implicate both CD11a and CD11b in that adhesion. In addition, we report that ICAM-1 mediates, in part, the initial leukocyte–endothelial cell adhesion following C5a exposure in vivo.