Platelet and endothelial cell P-selectin are required for host defense against Klebsiella pneumoniae-induced pneumosepsis.

BackgroundSepsis is associated with activation of platelets and endothelial cells accompanied by enhanced P-selectin surface expression. Both platelet- and endothelial P-selectin have been associated with leukocyte recruitment and induction of inflammatory alterations. Klebsiella (K.) pneumoniae is a common human sepsis pathogen, particularly in the context of pneumonia. MethodsWild-type (WT) and P-selectin-deficient (Selp(-/-)) mice or bone marrow chimeric mice were infected with K.pneumoniae via the airways to induce pneumosepsis. Mice were sacrificed during early (12h after infection) or late-stage (44h) sepsis for analyses, or followed in a survival study. ResultsSelp(-/-) mice displayed 10-1000-fold higher bacterial burdens in the lungs, blood and distant organs during late-stage sepsis. P-selectin deficiency did not influence leukocyte recruitment to the lungs, but was associated with decreased platelet-monocyte complexes and increased cytokine release. Bone marrow transfer studies revealed a role for both platelet and endothelial cell P-selectin as mice deficient in platelet or endothelial cell P-selectin displayed an intermediate phenotype in bacterial loads and survival compared with full wild-type or full knockout control mice. ConclusionBoth platelet and endothelial cell P-selectin contribute to host defense during Klebsiella pneumosepsis.