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Thrombocytopenia impairs host defense in gram-negative pneumonia-derived sepsis in mice.
Blood 2014; 124(25):3781-90Blood

Abstract

Thrombocytopenia is a common finding in sepsis and associated with a worse outcome. We used a mouse model of pneumonia-derived sepsis caused by the human pathogen Klebsiella pneumoniae to study the role of platelets in host response to sepsis. Platelet counts (PCs) were reduced to less than a median of 5 × 10(9)/L or to 5 to 13 × 10(9)/L by administration of a depleting antibody in mice infected with Klebsiella via the airways. Thrombocytopenia was associated with strongly impaired survival during pneumonia-derived sepsis proportional to the extent of platelet depletion. Thrombocytopenic mice demonstrated PC-dependent enhanced bacterial growth in lungs, blood, and distant organs. Severe thrombocytopenia resulted in hemorrhage at the primary site of infection, but not in distant organs. PCs of 5 to 13 × 10(9)/L were sufficient to largely maintain hemostasis in infected lungs. Thrombocytopenia did not influence lung inflammation or neutrophil recruitment and did not attenuate local or systemic activation of coagulation or the vascular endothelium. PCs <5 × 10(9)/L even resulted in enhanced coagulation and endothelial cell activation, which coincided with increased proinflammatory cytokine levels. In accordance, low PCs in whole blood enhanced Klebsiella-induced cytokine release in vitro. These data suggest that platelets play an important role in host defense to Klebsiella pneumosepsis.

Authors+Show Affiliations

Center for Infection and Immunity Amsterdam, Center for Experimental and Molecular Medicine.Center for Infection and Immunity Amsterdam, Center for Experimental and Molecular Medicine.Center for Infection and Immunity Amsterdam, Center for Experimental and Molecular Medicine.Center for Infection and Immunity Amsterdam, Center for Experimental and Molecular Medicine.Department of Pathology, and.Center for Infection and Immunity Amsterdam, Center for Experimental and Molecular Medicine, 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

25301709

Citation

de Stoppelaar, Sacha F., et al. "Thrombocytopenia Impairs Host Defense in Gram-negative Pneumonia-derived Sepsis in Mice." Blood, vol. 124, no. 25, 2014, pp. 3781-90.
de Stoppelaar SF, van 't Veer C, Claushuis TA, et al. Thrombocytopenia impairs host defense in gram-negative pneumonia-derived sepsis in mice. Blood. 2014;124(25):3781-90.
de Stoppelaar, S. F., van 't Veer, C., Claushuis, T. A., Albersen, B. J., Roelofs, J. J., & van der Poll, T. (2014). Thrombocytopenia impairs host defense in gram-negative pneumonia-derived sepsis in mice. Blood, 124(25), pp. 3781-90. doi:10.1182/blood-2014-05-573915.
de Stoppelaar SF, et al. Thrombocytopenia Impairs Host Defense in Gram-negative Pneumonia-derived Sepsis in Mice. Blood. 2014 Dec 11;124(25):3781-90. PubMed PMID: 25301709.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Thrombocytopenia impairs host defense in gram-negative pneumonia-derived sepsis in mice. AU - de Stoppelaar,Sacha F, AU - van 't Veer,Cornelis, AU - Claushuis,Theodora A M, AU - Albersen,Bregje J A, AU - Roelofs,Joris J T H, AU - van der Poll,Tom, Y1 - 2014/10/09/ PY - 2014/10/11/entrez PY - 2014/10/11/pubmed PY - 2015/2/24/medline SP - 3781 EP - 90 JF - Blood JO - Blood VL - 124 IS - 25 N2 - Thrombocytopenia is a common finding in sepsis and associated with a worse outcome. We used a mouse model of pneumonia-derived sepsis caused by the human pathogen Klebsiella pneumoniae to study the role of platelets in host response to sepsis. Platelet counts (PCs) were reduced to less than a median of 5 × 10(9)/L or to 5 to 13 × 10(9)/L by administration of a depleting antibody in mice infected with Klebsiella via the airways. Thrombocytopenia was associated with strongly impaired survival during pneumonia-derived sepsis proportional to the extent of platelet depletion. Thrombocytopenic mice demonstrated PC-dependent enhanced bacterial growth in lungs, blood, and distant organs. Severe thrombocytopenia resulted in hemorrhage at the primary site of infection, but not in distant organs. PCs of 5 to 13 × 10(9)/L were sufficient to largely maintain hemostasis in infected lungs. Thrombocytopenia did not influence lung inflammation or neutrophil recruitment and did not attenuate local or systemic activation of coagulation or the vascular endothelium. PCs <5 × 10(9)/L even resulted in enhanced coagulation and endothelial cell activation, which coincided with increased proinflammatory cytokine levels. In accordance, low PCs in whole blood enhanced Klebsiella-induced cytokine release in vitro. These data suggest that platelets play an important role in host defense to Klebsiella pneumosepsis. SN - 1528-0020 UR - https://www.unboundmedicine.com/medline/citation/25301709/Thrombocytopenia_impairs_host_defense_in_gram_negative_pneumonia_derived_sepsis_in_mice_ L2 - https://ashpublications.org/blood/article-lookup/doi/10.1182/blood-2014-05-573915 DB - PRIME DP - Unbound Medicine ER -