title: The role of selectins in VLA-4 and CD18-independent neutrophil migration to joints of rats with adjuvant arthritis.
abstract: Neutrophil migration from blood into inflamed tissues is mediated by adhesion molecules on neutrophils and on vascular endothelium. It was previously shown that the integrins VLA-4 and CD11/CD18 in combination mediate 70-80% of neutrophil recruitment to arthritic joints of rats. To investigate if the remaining recruitment involves the selectins, the effect of adhesion-blocking monoclonal antibodies (mAb) to each of the selectins (E-, P and L-), in combination with mAb to VLA-4 and CD18, on the migration of radiolabeled neutrophils to joints of rats with adjuvant arthritis was examined. Blocking P-selectin inhibited neutrophil accumulation in hindlimb joints by 40% whereas mAb to P- and E-selectin together inhibited the accumulation in all joints by 60% relative to anti-VLA-4 plus anti-CD18 treatment alone. Overall there was 90% inhibition relative to arthritic controls. Blocking E- or L-selectin alone or together had no effect. Our results demonstrate that P-selectin in particular and in concert with E-selectin are required for the VLA-4- and CD18-independent migration of neutrophils to sites of chronic arthritis in the rat.
authors.affiliation: Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: U
authors.initials: U
authors.lastname: Birner
authors.forename: T B
authors.initials: TB
authors.lastname: Issekutz
authors.forename: A C
authors.initials: AC
authors.lastname: Issekutz
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001169:Arthritis, Experimental / Q000276:immunology*; D018821:CD18 Antigens / Q000502:physiology*; D002465:Cell Movement; D039041:Integrin alpha4beta1; D016023:Integrins / Q000502:physiology*; D007596:Joints / Q000276:immunology*; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D016201:Receptors, Lymphocyte Homing / Q000502:physiology*; D019087:Selectins / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D039041:Integrin alpha4beta1; D016023:Integrins; D016201:Receptors, Lymphocyte Homing; D019087:Selectins