The role of Platelet Factor 4 in local and remote tissue damage in a mouse model of mesenteric ischemia/reperfusion injury (120.18)

Abstract

Abstract The robust inflammatory response that takes place during ischemia reperfusion injury (IR/I) recruits factors from both the innate and adaptive immune system. However the contribution of platelets and their products such as Platelet Factor 4 (PF4; CXCL4), during the pathogenesis of IR/I has not been thoroughly investigated. We show that a deficiency in PF4 protects mice from local and remote tissue damage after 30 minutes of mesenteric ischemia and 3 hours of reperfusion in PF4-/- mice compared to control B6 mice. This protection was independent from Ig or complement deposition in the tissues. However, neutrophil and monocyte infiltration was decreased in the lungs of PF4-/- mice compared with B6 control mice. Platelet-depleted B6 mice transfused with platelets from PF4-/- mice displayed reduced tissue damage compared with controls. In contrast, transfusion of B6 platelets into platelet depleted PF4-/- mice reconstituted damage in both intestine and lung tissue. We also show that PF4 may modulate the release of IgA. Interestingly, we show that PF4 expression on intestinal epithelial cells is increased after ischemia/reperfusion at both the mRNA and protein levels. In conclusion, these findings demonstrate that PF4 represents an important mediator of local and remote tissue damage.