Background: It has been widely known that platelets play an important role in inflammation, in addition to their function in hemostasis and thrombosis. On activation, platelets release various immune mediators including adhesion molecules which may induce and maintain inflammatory reactions. Recently we have reported that platelets are required for recruitment of leukocytes into murine inflamed skin in immediate hypersensitivity reaction and chronic dermatitis. However, the role of platelet-derived adhesion molecules in skin inflammation has not been understood yet.
Object: We investigated the role of platelet-derived adhesion molecules, P-selectin and junctional adhesion molecule (JAM)-A in a mouse model of contact hypersensitivity.
Methods: Mice were sensitized and hypersensitivity was elicited in ear skin with hapten, with or without platelet depletion by administration of antiplatelet antibody. Moreover, platelets from normal mice or platelets deficient with P-selectin or JAM-A were infused into platelet-depleted mice.
Results: In platelet-depleted mice, the ear-swelling response and leukocyte infiltration into skin significantly decreased. Flow cytometry showed that the number of platelet-leukocyte aggregates were higher in blood of hapten-challenged mice compared with sham-challenged mice. Recruitment of leukocytes to skin was restored by infusing platelets from normal mice, and this was blocked by infusing platelets from P-selectin-deficient mice or platelets pretreated with anti-P-selectin antibody. Moreover, infusion of platelets pretreated with anti-JAM-A antibody also suppressed leukocyte recruitment. A combination of both antibodies showed further decrease in leukocyte recruitment.
Conclusion: These results suggest that platelets induce leukocyte recruitment to skin by forming platelet-leukocyte aggregates via distinct sets of adhesion molecules P-selectin and JAM-A.