Inhibition of leukocyte extravasation with a monoclonal antibody to CD18 during formation of experimental intimal thickening in rabbit carotid arteries.
In the rabbit model of electrically induced intimal thickening, the adherence processes of different leukocyte subsets as well as the functional significance of leukocyte invasion in the initial migration of smooth muscle cells (SMCs) into the intima were studied by using monoclonal antibody (MAb) 60.3 (directed to the leukocyte adherence glycoprotein CD18), a known potent inhibitor of leukocyte adhesive functions. In control carotid arteries exposed to two periods of electrical stimulation within 36 hours, leukocytes, including all granulocyte subsets, monocytes, and lymphocytes, invaded the cell-free subendothelium. Concomitantly, SMCs were observed to migrate from the media into the intima. In the MAb 60.3-treated rabbits, however, neutrophil emigration into the stimulated arteries was abolished, whereas mononuclear leukocyte accumulation in the intima was only partially inhibited, indicating a complete CD18-dependent mechanism for neutrophil extravasation and additional receptor-ligand systems for the emigration of mononuclear leukocytes. SMCs moved into the intima despite complete blockage of neutrophils and the reduced accumulation of mononuclear cells within the subendothelium after MAb administration. These results preclude neutrophils as initiators of SMC migration into the intima. The influence of mononuclear cells on the migratory behavior of SMCs in intimal thickening formation, however, needs further elucidation.
Kling
D
D
Institute of Physiology, University of Tübingen, FRG.
Fingerle
J
J
Harlan
J M
JM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology*; D018845:CD11 Antigens; D018821:CD18 Antigens; D002339:Carotid Arteries / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000502:physiology; D002465:Cell Movement; D007958:Leukocyte Count; D007962:Leukocytes / Q000473:pathology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D011817:Rabbits; D019010:Vascular Cell Adhesion Molecule-1
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018845:CD11 Antigens; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D019010:Vascular Cell Adhesion Molecule-1