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

Summary Background Sepsis 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.) pneum...

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Veröffentlicht in:	Journal of thrombosis and haemostasis Jg. 13; H. 6; S. 1128 - 1138
Hauptverfasser:	Stoppelaar, S. F., Veer, C., Roelofs, J. J. T. H., Claushuis, T. A. M., Boer, O. J., Tanck, M. W. T., Hoogendijk, A. J., Poll, T.
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	England Elsevier Limited 01.06.2015
Schlagworte:	Animals Bacterial Load Blood Coagulation Blood Platelets - immunology Blood Platelets - metabolism Blood Platelets - microbiology Bone Marrow Transplantation Chemotaxis, Leukocyte Cytokines - blood Disease Models, Animal Endothelial Cells - immunology Endothelial Cells - metabolism Endothelial Cells - microbiology endothelium Host-Pathogen Interactions Immunity, Innate Inflammation Mediators - blood Klebsiella Infections - genetics Klebsiella Infections - immunology Klebsiella Infections - metabolism Klebsiella Infections - microbiology Klebsiella pneumoniae - growth & development Klebsiella pneumoniae - immunology Klebsiella pneumoniae - pathogenicity Lung - immunology Lung - metabolism Lung - microbiology Mice, Inbred C57BL Mice, Knockout P-Selectin - genetics P-Selectin - metabolism Platelet Activation platelets pneumonia Pneumonia, Bacterial - genetics Pneumonia, Bacterial - immunology Pneumonia, Bacterial - metabolism Pneumonia, Bacterial - microbiology Protective Factors P‐selectin sepsis Sepsis - genetics Sepsis - immunology Sepsis - metabolism Sepsis - microbiology Signal Transduction Time Factors endothelium pneumonia P-selectin platelets sepsis
ISSN:	1538-7933, 1538-7836, 1538-7836
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Zusammenfassung:	Summary Background Sepsis 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. Methods Wild‐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 (12 h after infection) or late‐stage (44 h) sepsis for analyses, or followed in a survival study. Results Selp−/− 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. Conclusion Both platelet and endothelial cell P‐selectin contribute to host defense during Klebsiella pneumosepsis.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	1538-7933 1538-7836 1538-7836
DOI:	10.1111/jth.12893