Crystalline Silica Impairs Efferocytosis Abilities of Human and Mouse Macrophages: Implication for Silica-Associated Systemic Sclerosis.

Frontiers in Immunology
Alain LescoatValérie Lecureur

Abstract

Inhalation of crystalline silica (SiO2) is a risk factor of systemic autoimmune diseases such as systemic sclerosis (SSc) and fibrotic pulmonary disorders such as silicosis. A defect of apoptotic cell clearance (i.e., efferocytosis, a key process in the resolution of inflammation) is reported in macrophages from patients with fibrotic or autoimmune diseases. However, the precise links between SiO2 exposure and efferocytosis impairment remain to be determined. Answering to this question may help to better link innate immunity and fibrosis. In this study, we first aim to determine whether SiO2 might alter efferocytosis capacities of human and mouse macrophages. We secondly explore possible mechanisms explaining efferocytosis impairment, with a specific focus on macrophage polarization and on the RhoA/ROCK pathway, a key regulator of cytoskeleton remodeling and phagocytosis. Human monocyte-derived macrophages (MDM) and C57BL/6J mice exposed to SiO2 and to CFSE-positive apoptotic Jurkat cells were analyzed by flow cytometry to determine their efferocytosis index (EI). The effects of ROCK inhibitors (Y27632 and Fasudil) on EI of SiO2-exposed MDM and MDM from SSc patients were evaluated in vitro. Our results demonstrated that SiO2 si...Continue Reading

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Citations

Sep 18, 2020·Current Opinion in Rheumatology·Vincent SobanskiDavid Launay
Oct 7, 2020·Rheumatology·Alain LescoatCatherine Cavalin
Dec 3, 2020·International Journal of Molecular Sciences·Anna ChiariniIlaria Dal Prà
Sep 10, 2020·Seminars in Arthritis and Rheumatism·Alice BallerieAlain Lescoat
May 1, 2021·International Journal of Molecular Sciences·Jana Adamcakova, Daniela Mokra
Jul 16, 2021·International Journal of Epidemiology·Alain LescoatValérie Lecureur
Sep 2, 2021·Clinical Reviews in Allergy & Immunology·Alain LescoatDinesh Khanna

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Datasets Mentioned

BETA
GM-CSF

Methods Mentioned

BETA
flow cytometry
Fluorescence
electrophoresis
Pull-Down
transfection

Software Mentioned

Image J
GraphPad
GraphPad Prism
ImageJ
FACSDiva

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