P-selectin-dependent leukocyte adhesion is governed by endolysosomal two-pore channel 2.

Autor:	Goretzko J; Research Group Cellular Biochemistry - Regulatory Mechanisms of Inflammation, Institute of Molecular Virology, Center for Molecular Biology of Inflammation, University of Muenster (formerly Research Group Regulatory Mechanisms of Inflammation, Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, University of Muenster), von-Esmarch-Strasse 56, 48149 Muenster, Germany., Pauels I; Research Group Cellular Biochemistry - Regulatory Mechanisms of Inflammation, Institute of Molecular Virology, Center for Molecular Biology of Inflammation, University of Muenster (formerly Research Group Regulatory Mechanisms of Inflammation, Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, University of Muenster), von-Esmarch-Strasse 56, 48149 Muenster, Germany., Heitzig N; Research Group Cellular Biochemistry - Regulatory Mechanisms of Inflammation, Institute of Molecular Virology, Center for Molecular Biology of Inflammation, University of Muenster (formerly Research Group Regulatory Mechanisms of Inflammation, Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, University of Muenster), von-Esmarch-Strasse 56, 48149 Muenster, Germany., Thomas K; Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Albert Schweitzer Campus 1, A1, 48149 Muenster, Germany., Kardell M; Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Albert Schweitzer Campus 1, A1, 48149 Muenster, Germany., Naß J; Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, University of Muenster, von-Esmarch-Strasse 56, 48149 Muenster, Germany., Krogsaeter EK; Walther-Straub-Institute for Pharmacology and Toxicology, Ludwig-Maximilians-University, Nussbaumstrasse 26, 80336 Munich, Germany., Schloer S; Research Group Cellular Biochemistry - Regulatory Mechanisms of Inflammation, Institute of Molecular Virology, Center for Molecular Biology of Inflammation, University of Muenster (formerly Research Group Regulatory Mechanisms of Inflammation, Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, University of Muenster), von-Esmarch-Strasse 56, 48149 Muenster, Germany., Spix B; Walther-Straub-Institute for Pharmacology and Toxicology, Ludwig-Maximilians-University, Nussbaumstrasse 26, 80336 Munich, Germany., Linard Matos AL; Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, University of Muenster, von-Esmarch-Strasse 56, 48149 Muenster, Germany., Leser C; Department of Pharmacy, Center for Drug Research, Ludwig-Maximilians-University, Butenandtstrasse 5-13, 81377 Munich, Germany., Wegner T; Institute of Organic Chemistry, University of Muenster, Corrensstrasse 40, 48149 Muenster, Germany., Glorius F; Institute of Organic Chemistry, University of Muenster, Corrensstrasse 40, 48149 Muenster, Germany., Bracher F; Department of Pharmacy, Center for Drug Research, Ludwig-Maximilians-University, Butenandtstrasse 5-13, 81377 Munich, Germany., Gerke V; Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, University of Muenster, von-Esmarch-Strasse 56, 48149 Muenster, Germany., Rossaint J; Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Albert Schweitzer Campus 1, A1, 48149 Muenster, Germany., Grimm C; Walther-Straub-Institute for Pharmacology and Toxicology, Ludwig-Maximilians-University, Nussbaumstrasse 26, 80336 Munich, Germany; Immunology, Infection and Pandemic Research IIP, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, 60596 Frankfurt am Main, Germany., Rescher U; Research Group Cellular Biochemistry - Regulatory Mechanisms of Inflammation, Institute of Molecular Virology, Center for Molecular Biology of Inflammation, University of Muenster (formerly Research Group Regulatory Mechanisms of Inflammation, Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, University of Muenster), von-Esmarch-Strasse 56, 48149 Muenster, Germany. Electronic address: rescher@uni-muenster.de.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2023 Dec 26; Vol. 42 (12), pp. 113501. Date of Electronic Publication: 2023 Nov 30.
DOI:	10.1016/j.celrep.2023.113501
Abstrakt:	Upon proinflammatory challenges, endothelial cell surface presentation of the leukocyte receptor P-selectin, together with the stabilizing co-factor CD63, is needed for leukocyte capture and is mediated via demand-driven exocytosis from the Weibel-Palade bodies that fuse with the plasma membrane. We report that neutrophil recruitment to activated endothelium is significantly reduced in mice deficient for the endolysosomal cation channel TPC2 and in human primary endothelial cells with pharmacological TPC2 block. We observe less CD63 signal in whole-mount stainings of proinflammatory-activated cremaster muscles from TPC2 knockout mice. We find that TPC2 is activated and needed to ensure the transfer of CD63 from endolysosomes via Weibel-Palade bodies to the plasma membrane to retain P-selectin on the cell surface of human primary endothelial cells. Our findings establish TPC2 as a key element to leukocyte interaction with the endothelium and a potential pharmacological target in the control of inflammatory leukocyte recruitment. Competing Interests: Declaration of interests The authors declare no competing interests. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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