Background: P-selectin promotes platelet aggregation, and platelet-leukocyte complex (PLC) formation via PSGL-1 binding, after activation. Patients with acute myocardial infarction show elevated PLC and predict adverse outcome. Yet, their pathomechanistic significance remains unclear.

Purpose: What is the relevance of platelet P-selectin exocytosis and P-selectin mediated PLC formation for myocardial ischemia and reperfusion injury.

Methods: Bl6J mice were irradiated and reconstituted with either P-selectin deficient (KO) or wild type (WT) bone marrow cells. P-selectin expression in endothelial cells remained unaffected. Given that P-selectin was only expressed by platelets in the blood this approach allowed us to test the specific function of platelet-derived P-selectin.

Results: Circulating PLC tripled and peaked within 24h of reperfusion following 35min of LAD ligation in mice. Circulating PLC were diminished by more than 70% following myocardial ischemia/reperfusion injury. Yet, leukocyte rolling and adhesion to the activated endothelium was similar in both groups, as was infiltration into sterile peritonitis. Likewise, myocardial infarct size, tissue inflammation and loss in cardiac function remained unaffected despite the lack of circulating and infiltrating PLC. In contrast, P-selectin on platelets supported the phagocytosis of E. coli and Staph. aureus bacterial particles by monocytes and neutrophils.

Conclusion: PLC formation is most likely triggered by inflammation due to myocardial ischemia. P-selectin dependent PLC formation has no influence on infarct size, cell migration or cardiac function after ischemia reperfusion injury. Increased numbers of circulating PLC are markers rather than mediators of cardiac damage. PLC formation seems to have a crucial role in bacterial phagocytosis.