The effect of anti-intercellular adhesion molecule-1 on phorbol-ester-induced rabbit lung inflammation.
The role of the CD18 complex of leukocyte glycoproteins in adhesion-dependent functions of human leukocytes in vitro has been well documented. A ligand, intercellular adhesion molecule-1 (ICAM-1), for at least one member of the CD18 complex has been identified. This molecule is inducible on many cell types including vascular endothelium and keratinocytes by inflammatory mediators such as IL-1, TNF, and IFN-gamma. ICAM-1 has been shown to mediate, in part, the in vitro adhesion of lymphocytes and neutrophils to endothelial cells expressing ICAM-1. In the present study we have shown that mAb's to the human CD18 complex and to human ICAM-1 cross react with rabbit cells and that both anti-CD18 and anti-CD11b but neither anti-CD11a nor anti-ICAM-1 mAb's inhibit neutrophil migration, an adhesion-dependent function, in vitro. Pretreatment of rabbits with anti-CD18 and anti-ICAM-1 but not anti-CD11a mAb inhibited by greater than 60% neutrophil migration into PMA-induced inflamed rabbit lungs. This effect of anti-ICAM-1 mAb on pulmonary neutrophil influx after PMA injection has important implications. Specifically, that ICAM-1 can function as a ligand for CD18 and can mediate, at least in part, the migration of neutrophils to inflammatory sites.
Barton
R W
RW
Department of Immunology, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877.
Rothlein
R
R
Ksiazek
J
J
Kennedy
C
C
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000502:physiology*; D000918:Antibody Specificity; D000954:Antigens, Surface / Q000276:immunology* / Q000502:physiology; D018821:CD18 Antigens; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules; D002465:Cell Movement / Q000187:drug effects; D003429:Cross Reactions; D006801:Humans; D007166:Immunosuppressive Agents / Q000276:immunology / Q000502:physiology; D008168:Lung / Q000276:immunology / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D011817:Rabbits; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D007166:Immunosuppressive Agents; D008562:Membrane Glycoproteins; D013755:Tetradecanoylphorbol Acetate