Modulation of neutrophil influx with cell adhesion molecule specific antibodies during nonspecific and immune mediated inflammatory reactions

Abstract

Neutrophils are essential for the host defence against infection. However, neutrophils may also mediate damage namely during immune mediated pathologies. We therefore tested whether targeting of different cell adhesion molecules with specific monoclonal antibodies might reduce immune mediated neutrophil recruitment but spare the nonspecific accumulation of neutrophils that is essential for the resistance against acute infections. Neutrophil recruitment was induced by either intraperitoneal injection of casein as a nonspecific phlogistic agent or by i.p. injection of antigen in Mycobacterium bovis Bacille Caimette-Guerin (BCG) immune mice. Similar degrees of inhibition of neutrophil accumulation were observed in both models of inflammation with antibodies directed at CD11a, ICAM-1 and CD11b with the latter showing the most marked effects. Individual targeting of selectins was without effect in immune mediated responses whereas targeting of L or E selectin inhibited nonspecific recruitment of neutrophils. This was apparently not owing to a dosage effect nor to a kinetic difference. The inhibitory effect of anti-CD11b antibodies was most likely as a result of activation of circulating neutrophils rather than the blocking of receptor-ligand interactions. We were therefore unable to selectively abrogate immune mediated neutrophil recruitment with the use of the antibodies selected in this study.