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

Jonas Goretzko; Inga Pauels; Nicole Heitzig; Katharina Thomas; Marina Kardell; Johannes Naß; Einar Kleinhans Krogsaeter; Sebastian Schloer; Barbara Spix; Anna Lívia Linard Matos; Charlotte Leser; Tristan Wegner; Frank Glorius; Franz Bracher; Volker Gerke; Jan Rossaint; Christian Grimm; Ursula Rescher

Cell Reports (Dec 2023)

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

Jonas Goretzko,
Inga Pauels,
Nicole Heitzig,
Katharina Thomas,
Marina Kardell,
Johannes Naß,
Einar Kleinhans Krogsaeter,
Sebastian Schloer,
Barbara Spix,
Anna Lívia Linard Matos,
Charlotte Leser,
Tristan Wegner,
Frank Glorius,
Franz Bracher,
Volker Gerke,
Jan Rossaint,
Christian Grimm,
Ursula Rescher

Affiliations

Jonas Goretzko: 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
Inga Pauels: 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
Nicole Heitzig: 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
Katharina Thomas: Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Albert Schweitzer Campus 1, A1, 48149 Muenster, Germany
Marina Kardell: Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Albert Schweitzer Campus 1, A1, 48149 Muenster, Germany
Johannes Naß: Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, University of Muenster, von-Esmarch-Strasse 56, 48149 Muenster, Germany
Einar Kleinhans Krogsaeter: Walther-Straub-Institute for Pharmacology and Toxicology, Ludwig-Maximilians-University, Nussbaumstrasse 26, 80336 Munich, Germany
Sebastian Schloer: 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
Barbara Spix: Walther-Straub-Institute for Pharmacology and Toxicology, Ludwig-Maximilians-University, Nussbaumstrasse 26, 80336 Munich, Germany
Anna Lívia Linard Matos: Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, University of Muenster, von-Esmarch-Strasse 56, 48149 Muenster, Germany
Charlotte Leser: Department of Pharmacy, Center for Drug Research, Ludwig-Maximilians-University, Butenandtstrasse 5-13, 81377 Munich, Germany
Tristan Wegner: Institute of Organic Chemistry, University of Muenster, Corrensstrasse 40, 48149 Muenster, Germany
Frank Glorius: Institute of Organic Chemistry, University of Muenster, Corrensstrasse 40, 48149 Muenster, Germany
Franz Bracher: Department of Pharmacy, Center for Drug Research, Ludwig-Maximilians-University, Butenandtstrasse 5-13, 81377 Munich, Germany
Volker Gerke: Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, University of Muenster, von-Esmarch-Strasse 56, 48149 Muenster, Germany
Jan Rossaint: Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Albert Schweitzer Campus 1, A1, 48149 Muenster, Germany
Christian Grimm: 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
Ursula Rescher: 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; Corresponding author

Journal volume & issue: Vol. 42, no. 12
p. 113501

Abstract

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Summary: 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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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