S F de Stoppelaar1,2, C Van't Veer1,2, J J T H Roelofs3, T A M Claushuis1,2, O J de Boer3, M W T Tanck4, A J Hoogendijk1,2, T van der Poll1,2,5. 1. Academic Medical Center, Center for Infection and Immunity Amsterdam (CINIMA), University of Amsterdam, Amsterdam, the Netherlands. 2. Academic Medical Center, Center for Experimental and Molecular Medicine (CEMM), University of Amsterdam, Amsterdam, the Netherlands. 3. Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. 4. Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, the Netherlands. 5. Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
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.
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 humansepsis 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: Chao Ding; Cornelis van 't Veer; Joris J T H Roelofs; Meenal Shukla; Keith R McCrae; Alexey S Revenko; Jeff Crosby; Tom van der Poll Journal: Am J Physiol Lung Cell Mol Physiol Date: 2017-11-09 Impact factor: 5.464
Authors: Theodora A M Claushuis; Alex F de Vos; Joris J T H Roelofs; Onno J de Boer; Cornelis van 't Veer; Tom van der Poll Journal: J Innate Immun Date: 2018-12-17 Impact factor: 7.349
Authors: Elizabeth A Middleton; Matthew T Rondina; Hansjorg Schwertz; Guy A Zimmerman Journal: Am J Respir Cell Mol Biol Date: 2018-07 Impact factor: 6.914
Authors: Emma Birnie; Gavin C K W Koh; Ester C Löwenberg; Joost C M Meijers; Rapeephan R Maude; Nicholas P J Day; Sharon J Peacock; Tom van der Poll; W Joost Wiersinga Journal: PLoS Negl Trop Dis Date: 2017-03-15