title: Single platelets seal neutrophil-induced vascular breaches via GPVI during immune-complex-mediated inflammation in mice.
abstract: Platelets protect vascular integrity during inflammation. Recent evidence suggests that this action is independent of thrombus formation and requires the engagement of glycoprotein VI (GPVI), but it remains unclear how platelets prevent inflammatory bleeding. We investigated whether platelets and GPVI act primarily by preventing detrimental effects of neutrophils using models of immune complex (IC)-mediated inflammation in mice immunodepleted in platelets and/or neutrophils or deficient in GPVI. Depletion of neutrophils prevented bleeding in thrombocytopenic and GPVI(-/-) mice during IC-mediated dermatitis. GPVI deficiency did not modify neutrophil recruitment, which was reduced by thrombocytopenia. Neutrophil cytotoxic activities were reduced in thrombocytopenic and GPVI(-/-) mice during IC-mediated inflammation. Intravital microscopy revealed that in this setting, intravascular binding sites for platelets were exposed by neutrophils, and GPVI supported the recruitment of individual platelets to these spots. Furthermore, the platelet secretory response accompanying IC-mediated inflammation was partly mediated by GPVI, and blocking of GPVI signaling impaired the vasculoprotective action of platelets. Together, our results show that GPVI plays a dual role in inflammation by enhancing neutrophil-damaging activities while supporting the activation and hemostatic adhesion of single platelets to neutrophil-induced vascular breaches.
authors.affiliation: INSERM Unit 1148, University Paris Diderot, Paris, France; Laboratory for Vascular Translational Science, Sorbonne Paris Cité, Paris, France;
authors.forename: Angèle
authors.initials: A
authors.lastname: Gros
authors.affiliation: INSERM Unit 1148, University Paris Diderot, Paris, France; Laboratory for Vascular Translational Science, Sorbonne Paris Cité, Paris, France;
authors.forename: Varouna
authors.initials: V
authors.lastname: Syvannarath
authors.affiliation: INSERM Unit 1148, University Paris Diderot, Paris, France; Laboratory for Vascular Translational Science, Sorbonne Paris Cité, Paris, France;
authors.forename: Lamia
authors.initials: L
authors.lastname: Lamrani
authors.affiliation: INSERM Unit 1148, University Paris Diderot, Paris, France; Laboratory for Vascular Translational Science, Sorbonne Paris Cité, Paris, France;
authors.forename: Véronique
authors.initials: V
authors.lastname: Ollivier
authors.affiliation: INSERM Unit 1148, University Paris Diderot, Paris, France; Laboratory for Vascular Translational Science, Sorbonne Paris Cité, Paris, France;
authors.forename: Stéphane
authors.initials: S
authors.lastname: Loyau
authors.affiliation: Department of Dermatology, University Hospital of Münster, Münster, Germany; Interdisciplinary Center for Clinical Research (IZKF), University of Münster, Münster, Germany; and.
authors.forename: Tobias
authors.initials: T
authors.lastname: Goerge
authors.affiliation: Department of Vascular Medicine, University Hospital and Rudolf Virchow Center, Würzburg, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Nieswandt
authors.affiliation: INSERM Unit 1148, University Paris Diderot, Paris, France; Laboratory for Vascular Translational Science, Sorbonne Paris Cité, Paris, France;
authors.forename: Martine
authors.initials: M
authors.lastname: Jandrot-Perrus
authors.affiliation: INSERM Unit 1148, University Paris Diderot, Paris, France; Laboratory for Vascular Translational Science, Sorbonne Paris Cité, Paris, France;
authors.forename: Benoît
authors.identifier: http://orcid.org/0000-0002-7428-1760
authors.initials: B
authors.lastname: Ho-Tin-Noé
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D004195:Disease Models, Animal; D007105:Immune Complex Diseases / Q000150:complications / Q000473:pathology*; D007249:Inflammation / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000473:pathology*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*
chemical_list: D018836:Inflammation Mediators; D010980:Platelet Membrane Glycoproteins; C098341:platelet membrane glycoprotein VI