title: The role of E- and P-selectin in neutrophil and monocyte migration in adjuvant-induced arthritis in the rat.
abstract: The role of the endothelial adhesion molecules E- and P-selectin in leukocyte accumulation in arthritis is not known. We investigated this role in rat adjuvant arthritis by employing adhesion function-blocking monoclonal antibodies (mAb) to rat P- and E-selectin. The acute migration (2 h) of radiolabeled rat blood neutrophils and monocytes to joints and skin was determined. Anti-P-selectin mAb significantly reduced accumulation of monocytes (by 50%) and neutrophils (by 40%) in the talar joint, and of neutrophils in tail joints (by 90%). Anti-E-selectin mAb alone did not attenuate leukocyte migration, but when combined with anti-P-selectin mAb, it enhanced inhibition of neutrophil accumulation in the talar and carpal joints. In the same animals, anti-P-selectin mAb significantly inhibited neutrophil and monocyte migration to dermal inflammatory reactions induced by zymosan-activated rat serum (ZAS) containing the chemotactic factor C5ades Arg, endotoxin (LPS), interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). In contrast, anti-E-selectin mAb alone had no effect on monocyte or neutrophil accumulation in inflamed skin of arthritic animals, but again enhanced the inhibition when combined with mAb to P-selectin. The addition of anti-L-selectin mAb to anti-P- and E-selectin mAb did not further suppress monocyte or neutrophil migration to inflamed skin or joints. These results demonstrate that optimal leukocyte migration to arthritic joints and inflamed skin is P-selectin dependent, and E-selectin is not essential. However, E-selectin contributes to migration when P-selectin mechanisms are not operative. L-selectin does not play a role in E- and P-selectin-independent leukocyte migration to joints or skin inflammation in arthritic rats. However, it is likely that additional selectin-independent pathways also mediate neutrophil and monocyte migration to joint and skin inflammation.
authors.affiliation: Department Pediatrics and Microbiology-Immunology, Dalhousie University, Halifax, Canada.
authors.forename: U M
authors.initials: UM
authors.lastname: Walter
authors.forename: A C
authors.initials: AC
authors.lastname: Issekutz
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D003872:Dermatitis / Q000276:immunology / Q000473:pathology / Q000628:therapy; D019040:E-Selectin / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D007275:Injections, Intravenous; D007596:Joints / Q000473:pathology; D019041:L-Selectin / Q000276:immunology; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D009161:Mycobacterium / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D019007:P-Selectin / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D000911:Antibodies, Monoclonal; D019040:E-Selectin; D019007:P-Selectin; D019041:L-Selectin