Impaired adhesion of neutrophils expressing Slc44a2/HNA-3b to VWF protects against NETosis under venous shear rates

Autor: Gaia Zirka, Paulette Legendre, Bart J.M. van Vlijmen, Philippe Robert, Victoria Tishkova, Chrissta X. Maracle, Peter J. Lenting, Grace M. Thomas, Julia Tilburg, Marie-Christine Alessi, Pierre-Emmanuel Morange
Přispěvatelé: Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Adhésion et Inflammation (LAI), Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM), Universiteit Leiden [Leiden], Centre Interdisciplinaire de Nanoscience de Marseille (CINaM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des Interactions Ecotoxicologie, Biodiversité, Ecosystèmes (LIEBE), Université Paul Verlaine - Metz (UPVM)-Centre National de la Recherche Scientifique (CNRS), Trombosestichting Nederland (#2015-4), ANR-17-CE14-0003,CLINT,Determination des fonctions de CTL2 dans la thrombose(2017), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Leiden University Medical Center (LUMC), Universiteit Leiden, Hémostase, Inflammation, Thrombose (HITH - U1176 Inserm - CHU Bicêtre), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)-Université Paris-Saclay, Hôpital de la Timone [CHU - APHM] (TIMONE)
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Male
Isoantigens
Lipopolysaccharide
Neutrophils
Immunology
Gene Expression
Inflammation
030204 cardiovascular system & hematology
Biochemistry
Extracellular Traps
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Von Willebrand factor
[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
von Willebrand Factor
[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB]
medicine
Cell Adhesion
Animals
Humans
Receptor
Cells
Cultured
Venous Thrombosis
Membrane Glycoproteins
biology
Degranulation
Membrane Transport Proteins
[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology
Cell Biology
Hematology
Adhesion
Neutrophil extracellular traps
Molecular biology
Mice
Inbred C57BL
030104 developmental biology
HEK293 Cells
chemistry
Blood Circulation
biology.protein
medicine.symptom
Intravital microscopy
Zdroj: Blood
Blood, American Society of Hematology, 2021, 137 (16), pp.2256-2266. ⟨10.1182/blood.2020008345⟩
Blood, 137(16), 2256-2266. AMER SOC HEMATOLOGY
Blood, 2021, 137 (16), pp.2256-2266. ⟨10.1182/blood.2020008345⟩
ISSN: 0006-4971
1528-0020
Popis: Genome-wide association studies linked expression of the human neutrophil antigen 3b (HNA-3b) epitope on the Slc44a2 protein with a 30% decreased risk of venous thrombosis (VT) in humans. Slc44a2 is a ubiquitous transmembrane protein identified as a receptor for von Willebrand factor (VWF). To explain the link between Slc44a2 and VT, we wanted to determine how Slc44a2 expressing either HNA-3a or HNA-3b on neutrophils could modulate their adhesion and activation on VWF under flow. Transfected HEK293T cells or neutrophils homozygous for the HNA-3a– or HNA-3b–coding allele were purified from healthy donors and perfused in flow chambers coated with VWF at venous shear rates (100 s−1). HNA-3a expression was required for Slc44a2-mediated neutrophil adhesion to VWF at 100 s−1. This adhesion could occur independently of β2 integrin and was enhanced when neutrophils were preactivated with lipopolysaccharide. Moreover, specific shear conditions with high neutrophil concentration could act as a “second hit,” inducing the formation of neutrophil extracellular traps. Neutrophil mobilization was also measured by intravital microscopy in venules from SLC44A2-knockout and wild-type mice after histamine-induced endothelial degranulation. Mice lacking Slc44a2 showed a massive reduction in neutrophil recruitment in inflamed mesenteric venules. Our results show that Slc44a2/HNA-3a is important for the adhesion and activation of neutrophils in veins under inflammation and when submitted to specific shears. The fact that neutrophils expressing Slc44a2/HNA-3b have a different response on VWF in the conditions tested could thus explain the association between HNA-3b and a reduced risk for VT in humans.
Databáze: OpenAIRE
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