title: Platelet and endothelial cell P-selectin are required for host defense against Klebsiella pneumoniae-induced pneumosepsis.
abstract: 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.
  
  
  CONCLUSIONS
  Both platelet and endothelial cell P-selectin contribute to host defense during Klebsiella pneumosepsis.
authors.affiliation: Academic Medical Center, Center for Infection and Immunity Amsterdam (CINIMA), University of Amsterdam, Amsterdam, the Netherlands.|Academic Medical Center, Center for Experimental and Molecular Medicine (CEMM), University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: S F
authors.initials: SF
authors.lastname: de Stoppelaar
authors.affiliation: Academic Medical Center, Center for Infection and Immunity Amsterdam (CINIMA), University of Amsterdam, Amsterdam, the Netherlands.|Academic Medical Center, Center for Experimental and Molecular Medicine (CEMM), University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Van't Veer
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: J J T H
authors.initials: JJ
authors.lastname: Roelofs
authors.affiliation: Academic Medical Center, Center for Infection and Immunity Amsterdam (CINIMA), University of Amsterdam, Amsterdam, the Netherlands.|Academic Medical Center, Center for Experimental and Molecular Medicine (CEMM), University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: T A M
authors.initials: TA
authors.lastname: Claushuis
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: O J
authors.initials: OJ
authors.lastname: de Boer
authors.affiliation: Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: M W T
authors.initials: MW
authors.lastname: Tanck
authors.affiliation: Academic Medical Center, Center for Infection and Immunity Amsterdam (CINIMA), University of Amsterdam, Amsterdam, the Netherlands.|Academic Medical Center, Center for Experimental and Molecular Medicine (CEMM), University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: A J
authors.initials: AJ
authors.lastname: Hoogendijk
authors.affiliation: Academic Medical Center, Center for Infection and Immunity Amsterdam (CINIMA), University of Amsterdam, Amsterdam, the Netherlands.|Academic Medical Center, Center for Experimental and Molecular Medicine (CEMM), University of Amsterdam, Amsterdam, the Netherlands.|Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000818:Animals; D058491:Bacterial Load; D001777:Blood Coagulation; D001792:Blood Platelets / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D016026:Bone Marrow Transplantation; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D054884:Host-Pathogen Interactions; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000097:blood; D007710:Klebsiella Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity*; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism*; D015539:Platelet Activation; D018410:Pneumonia, Bacterial / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D065840:Protective Factors; D018805:Sepsis / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D019007:P-Selectin
keywords: P-selectin; endothelium; platelets; pneumonia; sepsis