ANTI-CD43 INHIBITS MONOCYTE-ENDOTHELIAL ADHESION IN INFLAMMATION AND ATHEROGENESIS

Recruitment of blood monocytes into tissues is a central event in the inflammatory response and in atherogenesis, The mechanisms leading to monocyte adhesion and migration through endothelium are not completely defined. We recently reported that MAb L11, against the leukocyte sia lomucin CD43, blocks T-lymphocyte binding to lymph node and Peyer's pa tch high endothelial venules (HEV) and inhibits T-cell extravasation f rom the blood into organized secondary lymphoid tissues, We have now a ssessed the ability of L11 to inhibit monocyte-endothelial (EC) intera ctions and trafficking, L11 blocks binding of WEH178/24 cells, a murin e monocytoid cell line, to inflamed lymph node HEV and inhibits recrui tment of monocytes and neutrophils to thioglycollate-inflamed peritone um. Because monocyte adhesion to the endothelium and diapedesis in les ion-prone regions of the vasculature is among the earliest events in a therogenesis, leading to formation of lipid-laden foam cells, the abil ity of L11 to block monocyte recognition of aortic endothelial cells w as assessed in a novel ex vivo assay of monocyte binding to intact rab bit aortic endothelium. Cholesterol feeding of rabbits induces enhance d aortic adhesiveness for monocytes and WEH178/24 monocytoid cells, an d this adhesion is inhibited by L11. The inhibitory effect of L11 is a dditive with that of a cocktail of anti-L-selectin and anti-al and bet a 2 integrin monoclonal antibodies. Thus, CD43 represents a novel targ et for manipulation of monocyte recruitment in inflammation and athero genesis. (C) 1997 by The American Society of Hematology.