Immune complex (IC)-induced tissue injury is mediated by inflammatory cell infiltration that is highly regulated by various adhesion molecules. To assess the contribution of
P-selectin glycoprotein ligand-1 (PSGL-1) and
selectins in the pathogenetic process, the cutaneous reverse-passive
Arthus reaction was examined in mice treated with
monoclonal antibodies (mAb) to PSGL-1 or P- and/or
E-selectin.
Edema and
hemorrhage were significantly reduced in mice treated with anti-
P-selectin mAb compared with control mice while they were not inhibited in mice treated with anti-
E-selectin mAb. It is remarkable that blocking PSGL-1 by mAb resulted in significant, further reduction in
edema and
hemorrhage compared with blocking anti-P- or anti-
E-selectin. However, blockade of E- and P-
selectins exhibited more significant reduction relative to PSGL-1 blockade. The inhibited
edema and
hemorrhage paralleled reduced infiltration of neutrophils and mast cells. Reduced infiltration of neutrophils and mast cells was observed in the peritoneal
Arthus reaction and was associated with the decreased production of
tumor necrosis factor alpha and
interleukin-6. The results of this study indicate that PSGL-1 contributes to the
Arthus reaction mainly as a
ligand of
P-selectin and partly as a
ligand of E- and/or
L-selectin by regulating neutrophil and mast-cell recruitment and that PSGL-1 would be a therapeutic target for human IC-mediated diseases.