The role of selectins in VLA-4 and CD18-independent neutrophil migration to joints of rats with adjuvant arthritis

Neutrophil migration from blood into inflamed tissues is mediated by adhesi on molecules on neutrophils and on vascular endothelium. It was previously shown that the integrins VLA-LF 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-bl ocking 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 radiolabele d neutrophils to joints of rats with adjuvant arthritis was examined. Block ing P-selectin inhibited neutrophil accumulation in hindlimb joints by 40 % whereas mAb to P- acid E-selectin together inhibited the accumulation in a ll joints by 60 % relative to anti-VLA-4 plus anti-CD18 treatment alone. Ov erall there was 90 % inhibition relative to arthritic controls. Blocking E- or L-selectin alone or together had no effect. Our results demonstrate tha t 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 chroni c arthritis in the rat.