학술논문
Caspase Inhibition Modulates Monocyte-Derived Macrophage Polarization in Damaged Tissues.
Document Type
Article
Author
Solier, Stéphanie; Mondini, Michele; Meziani, Lydia; Jacquel, Arnaud; Lacout, Catherine; Berghe, Tom Vanden; Julé, Yvon; Martinou, Jean-Claude; Pierron, Gérard; Rivière, Julie; Deloger, Marc; Dupuy, Corinne; Slama-Schwok, Anny; Droin, Nathalie; Vandenabeele, Peter; Auberger, Patrick; Deutsch, Eric; El-Benna, Jamel; Dang, Pham My-Chan; Solary, Eric
Source
Subject
*CASPASES
*NICOTINAMIDE adenine dinucleotide phosphate
*MONOCYTES
*SUPEROXIDES
*MACROPHAGES
*MACROPHAGE colony-stimulating factor
*CHRONIC granulomatous disease
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Language
ISSN
1661-6596
Abstract
Circulating monocytes are recruited in damaged tissues to generate macrophages that modulate disease progression. Colony-stimulating factor-1 (CSF-1) promotes the generation of monocyte-derived macrophages, which involves caspase activation. Here, we demonstrate that activated caspase-3 and caspase-7 are located to the vicinity of the mitochondria in CSF1-treated human monocytes. Active caspase-7 cleaves p47PHOX at aspartate 34, which promotes the formation of the NADPH (nicotinamide adenine dinucleotide phosphate) oxidase complex NOX2 and the production of cytosolic superoxide anions. Monocyte response to CSF-1 is altered in patients with a chronic granulomatous disease, which are constitutively defective in NOX2. Both caspase-7 down-regulation and radical oxygen species scavenging decrease the migration of CSF-1-induced macrophages. Inhibition or deletion of caspases prevents the development of lung fibrosis in mice exposed to bleomycin. Altogether, a non-conventional pathway that involves caspases and activates NOX2 is involved in CSF1-driven monocyte differentiation and could be therapeutically targeted to modulate macrophage polarization in damaged tissues. [ABSTRACT FROM AUTHOR]