Mast cells drive pathologic vascular lesions in Takayasu arteritis

Autor: Jean-Marie Launay, David Klatzmann, Aurélie S. Leroyer, D. Saadoun, Ulrich Blank, Paul Régnier, Alexandre Le Joncour, Gilles Kaplanski, Michelle Rosenzwajg, Anna Maciejewski-Duval, Anne-Claire Desbois, Patrice Cacoub, Fabien Koskas, Edwige Tellier, Michel Arock, Patrick Bruneval, Laurent Chiche, Mohamed Jarraya, Stéphane Barete, Cloé Comarmond, Pierre Fouret
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), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Imagerie médicale et quantitative, Center of Research on Inflammation, INSERM UMR S1149 and Centre National de la Recherche Scientifique Experimental Research Laboratory 8252, Universite de Paris, Sorbonne Paris Cite, Laboratoire d'Excellence INFLAMEX, Paris, France
Rok vydání: 2020
Předmět:
0301 basic medicine
Male
Pathology
Platelet-derived growth factor
Angiogenesis
[SDV]Life Sciences [q-bio]
Vascular permeability
chemistry.chemical_compound
0302 clinical medicine
Fibrosis
Immunology and Allergy
Mast Cells
ComputingMilieux_MISCELLANEOUS
Aorta
Cells
Cultured
Large vessel vasculitis
Middle Aged
Mast cell
Endothelial stem cell
medicine.anatomical_structure
[SDV.IMM]Life Sciences [q-bio]/Immunology
Female
Adult
medicine.medical_specialty
vascular remodeling
Immunology
Neovascularization
Physiologic
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Collagen Type I
Capillary Permeability
03 medical and health sciences
medicine.artery
medicine
Human Umbilical Vein Endothelial Cells
Animals
Humans
Takayasu
business.industry
Fibroblasts
medicine.disease
Interleukin-33
Takayasu Arteritis
Actins
Mice
Mutant Strains
Fibronectins
Mice
Inbred C57BL
030104 developmental biology
chemistry
business
mast cell
030215 immunology
Zdroj: Journal of Allergy and Clinical Immunology
Journal of Allergy and Clinical Immunology, Elsevier, 2021, ⟨10.1016/j.jaci.2021.05.003⟩
Journal of Allergy and Clinical Immunology, 2022, 149 (1), pp.292-301.e3. ⟨10.1016/j.jaci.2021.05.003⟩
Journal of Allergy and Clinical Immunology, 2022, 149 (1), ⟨10.1016/j.jaci.2021.05.003⟩
ISSN: 1097-6825
0091-6749
Popis: International audience; Background: Takayasu arteritis (TAK) is a large vessel vasculitis resulting in artery wall remodeling with segmental stenosis and/or aneurysm formation. Mast cells (MCs) are instrumental in bridging cell injury and inflammatory response.Objectives: This study sought to investigate the contribution of MCs on vessel permeability, angiogenesis, and fibrosis in patients with TAK. Methods: MC activation and their tissue expression were assessed in sera and in aorta from patients with TAK and from healthy donors (HDs). In vivo permeability was assessed using a modified Miles assay. Subconfluent cultured human umbilic vein endothelial cells and fibroblasts were used in vitro to investigate the effects of MC mediators on angiogenesis and fibrogenesis.Results: This study found increased levels of MC activation markers (histamine and indoleamine 2,3-dioxygenase) in sera of patients with TAK compared with in sera of HDs. Marked expression of MCs was shown in aortic lesions of patients with TAK compared with in those of noninflammatory aorta controls. Using Miles assay, this study showed that sera of patients with TAK significantly increased vascular permeability in vivo as compared with that of HDs. Vessel permeability was abrogated in MC-deficient mice. MCs stimulated by sera of patients with TAK supported neoangiogenesis (increased human umbilic vein endothelial cell proliferation and branches) and fibrosis by inducing increased production of fibronectin, type 1 collagen, and a-smooth muscle actin by fibroblasts as compared to MCs stimulated by sera of HD.Conclusions: MCs are a key regulator of vascular lesions in patients with TAK and may represent a new therapeutic target in large vessel vasculitis.
Databáze: OpenAIRE
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