Platelet Btk is Required for Maintaining Lung Vascular Integrity during Murine Pneumococcal Pneumosepsis.

Autor: de Porto APNA; Center for Experimental and Molecular Medicine (CEMM), Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.; Amsterdam Infection and Immunity Institute (AI&II), Amsterdam UMC, Amsterdam, The Netherlands., Claushuis TAM; Center for Experimental and Molecular Medicine (CEMM), Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.; Amsterdam Infection and Immunity Institute (AI&II), Amsterdam UMC, Amsterdam, The Netherlands., van der Donk LEH; Center for Experimental and Molecular Medicine (CEMM), Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.; Amsterdam Infection and Immunity Institute (AI&II), Amsterdam UMC, Amsterdam, The Netherlands., de Beer R; Center for Experimental and Molecular Medicine (CEMM), Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.; Amsterdam Infection and Immunity Institute (AI&II), Amsterdam UMC, Amsterdam, The Netherlands., de Boer OJ; Department of Pathology, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands., Florquin S; Department of Pathology, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands., Roelofs JJTH; Department of Pathology, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands., Hendriks RW; Department of Pulmonary Medicine, Erasmus MC Rotterdam, Rotterdam, The Netherlands., van der Poll T; Center for Experimental and Molecular Medicine (CEMM), Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.; Amsterdam Infection and Immunity Institute (AI&II), Amsterdam UMC, Amsterdam, The Netherlands.; Division of Infectious Diseases, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands., Van't Veer C; Center for Experimental and Molecular Medicine (CEMM), Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.; Amsterdam Infection and Immunity Institute (AI&II), Amsterdam UMC, Amsterdam, The Netherlands., de Vos AF; Center for Experimental and Molecular Medicine (CEMM), Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.; Amsterdam Infection and Immunity Institute (AI&II), Amsterdam UMC, Amsterdam, The Netherlands.
Jazyk: angličtina
Zdroj: Thrombosis and haemostasis [Thromb Haemost] 2019 Jun; Vol. 119 (6), pp. 930-940. Date of Electronic Publication: 2019 Mar 14.
DOI: 10.1055/s-0039-1681046
Abstrakt: Platelet Bruton's tyrosine kinase (Btk) is an essential signalling protein for the collagen receptor glycoprotein VI (GPVI) and podoplanin receptor C-type-lectin-like receptor-2, which are platelet receptors implicated in the maintenance of vascular integrity during inflammation. Moreover, platelets, platelet GPVI and Btk are important for host defence during murine bacterial pneumosepsis. The aim of this study was to determine the role of platelet Btk in vascular integrity and host defence during murine pneumosepsis caused by the common human pathogens Streptococcus pneumoniae and Klebsiella pneumoniae . Using the Cre-loxP system, male platelet-specific Btk-deficient mice (PF4creBtk fl /Y) were created. Similar to platelets from total Btk-deficient mice, platelets from PF4creBtk fl /Y mice showed abrogated aggregation and P-selectin expression when stimulated with the GPVI ligand cross-linked collagen-related peptide. Upon infection with S. pneumoniae , PF4creBtk fl /Y mice showed increased lung bleeding, but unimpaired anti-bacterial defence. During pneumosepsis evoked by K. pneumoniae , platelet Btk deficiency was not associated with lung bleeding and did not impact on host defence, even when platelet function was further compromised by blocking secondary platelet activation by the P2Y 12 receptor antagonist clopidogrel. Together, these data indicate that, while platelet Btk is not important for anti-bacterial defence in pneumosepsis, its role in maintaining vascular integrity in the lung depends on the causative pathogen.
Competing Interests: None declared.
(Georg Thieme Verlag KG Stuttgart · New York.)
Databáze: MEDLINE
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