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 sialomucin CD43, blocks T-lymphocyte binding to lymph node and Peyer's patch high endothelial venules (HEV) and inhibits T-cell extravasation from the blood into organized secondary lymphoid tissues. We have now assessed the ability of L11 to inhibit monocyte-endothelial (EC) interactions and trafficking. L11 blocks binding of WEHI78/24 cells, a murine monocytoid cell line, to inflamed lymph node HEV and inhibits recruitment of monocytes and neutrophils to thioglycollate-inflamed peritoneum. Because monocyte adhesion to the endothelium and diapedesis in lesion-prone regions of the vasculature is among the earliest events in atherogenesis, leading to formation of lipid-laden foam cells, the ability of L11 to block monocyte recognition of aortic endothelial cells was assessed in a novel ex vivo assay of monocyte binding to intact rabbit aortic endothelium. Cholesterol feeding of rabbits induces enhanced aortic adhesiveness for monocytes and WEHI78/24 monocytoid cells, and this adhesion is inhibited by L11. The inhibitory effect of L11 is additive with that of a cocktail of anti-L-selectin and anti-alpha4 and beta2 integrin monoclonal antibodies. Thus, CD43 represents a novel target for manipulation of monocyte recruitment in inflammation and atherogenesis.
McEvoy
L M
LM
Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University, Stanford, CA 94305, USA.
Jutila
M A
MA
Tsao
P S
PS
Cooke
J P
JP
Butcher
E C
EC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology; D015703:Antigens, CD; D001161:Arteriosclerosis / Q000276:immunology / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D004036:Diet, Atherogenic; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology*; D007249:Inflammation / Q000276:immunology / Q000473:pathology*; D051917:Leukosialin; D008297:Male; D051379:Mice; D009000:Monocytes / Q000276:immunology / Q000473:pathology*; D011817:Rabbits; D012795:Sialoglycoproteins / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D051917:Leukosialin; D012795:Sialoglycoproteins; C497863:Spn protein, mouse