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Platelet and endothelial cell P-selectin are required for host defense against Klebsiella pneumoniae-induced pneumosepsis.
J Thromb Haemost 2015; 13(6):1128-38JT

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.

CONCLUSION

Both platelet and endothelial cell P-selectin contribute to host defense during Klebsiella pneumosepsis.

Authors+Show Affiliations

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.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.Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.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.Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, the Netherlands.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.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.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25773400

Citation

de Stoppelaar, S F., et al. "Platelet and Endothelial Cell P-selectin Are Required for Host Defense Against Klebsiella Pneumoniae-induced Pneumosepsis." Journal of Thrombosis and Haemostasis : JTH, vol. 13, no. 6, 2015, pp. 1128-38.
de Stoppelaar SF, Van't Veer C, Roelofs JJ, et al. Platelet and endothelial cell P-selectin are required for host defense against Klebsiella pneumoniae-induced pneumosepsis. J Thromb Haemost. 2015;13(6):1128-38.
de Stoppelaar, S. F., Van't Veer, C., Roelofs, J. J., Claushuis, T. A., de Boer, O. J., Tanck, M. W., ... van der Poll, T. (2015). Platelet and endothelial cell P-selectin are required for host defense against Klebsiella pneumoniae-induced pneumosepsis. Journal of Thrombosis and Haemostasis : JTH, 13(6), pp. 1128-38. doi:10.1111/jth.12893.
de Stoppelaar SF, et al. Platelet and Endothelial Cell P-selectin Are Required for Host Defense Against Klebsiella Pneumoniae-induced Pneumosepsis. J Thromb Haemost. 2015;13(6):1128-38. PubMed PMID: 25773400.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Platelet and endothelial cell P-selectin are required for host defense against Klebsiella pneumoniae-induced pneumosepsis. AU - de Stoppelaar,S F, AU - Van't Veer,C, AU - Roelofs,J J T H, AU - Claushuis,T A M, AU - de Boer,O J, AU - Tanck,M W T, AU - Hoogendijk,A J, AU - van der Poll,T, Y1 - 2015/04/23/ PY - 2014/12/11/received PY - 2015/03/01/accepted PY - 2015/3/17/entrez PY - 2015/3/17/pubmed PY - 2016/2/26/medline KW - P-selectin KW - endothelium KW - platelets KW - pneumonia KW - sepsis SP - 1128 EP - 38 JF - Journal of thrombosis and haemostasis : JTH JO - J. Thromb. Haemost. VL - 13 IS - 6 N2 - 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. SN - 1538-7836 UR - https://www.unboundmedicine.com/medline/citation/25773400/Platelet_and_endothelial_cell_P_selectin_are_required_for_host_defense_against_Klebsiella_pneumoniae_induced_pneumosepsis_ L2 - https://doi.org/10.1111/jth.12893 DB - PRIME DP - Unbound Medicine ER -