Background: P-selectin is an adhesion molecule expressed on activated platelets and endothelial cells. While endothelial derived P-selectin is important for the initiation of leukocyte rolling, platelet derived P-selectin is thought to promote platelet-platelet and platelet-leukocyte aggregation. Circulating platelet-neutrophil and platelet-monocyte complexes (PNC, PMC) increase in inflammation and in patients with myocardial infarction, in particular. Yet, their functional relevance remains unclear to date.
Purpose: In this study we tested the importance of P-selectin dependent PLC formation and its impact on myocardial infarction.
Methods and Results: Bl6 mice were irradiated and reconstituted with either P-selectin deficient 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. Circulating platelet-leukocyte complexes were diminished by 60-80% at baseline and under inflammatory conditions. Still, leukocyte rolling and adhesion to the activated endothelium was similar in both groups as assessed by intravital microscopy. Likewise, similar numbers of neutrophils and monocytes accumulated in the sterile peritonitis lavage and myocardial infarct tissue although PLC were significantly reduced in P-selectin deficient chimeras.
Conclusion: P-selectin dependent platelet-leukocyte complex formation is dispensable for leukocyte recruitment to sites of inflammation. Our data suggest that PLC are mere biomarkers of inflammation without a genuine pathogenetic relevance in myocardial infarction.