Analysis of platelets and cell adhesion molecules as therapeutic targets in the immune-complex diseases

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To assess the role of platelets in the immune-complex diseases, the cutaneous Arthus reaction was examined in wild type mice and mice lacking E-selectin, P-selectin, or P-selectin glycoprotein ligand-1 (PSGL-1) with or without platelet depletion by busulfan. Edema and hemorrhage induced by immune complex challenge significantly decreased in busulfan-treated wild type mice compared with untreated mice. Busulfan treatment did not affect edema and hemorrhage in P-selectin- or PSGL-1-deficient mice, suggesting that the effect by busulfan is dependent on P-selectin and PSGL-1 expression. These results suggest that platelets induce leukocyte recruitment into skin by forming platelet-leukocyte aggregates and secreting chemokines at inflamed sites.