title: CD36, but not G2A, modulates efferocytosis, inflammation, and fibrosis following bleomycin-induced lung injury.
abstract: Macrophage G2A and CD36 lipid receptors are thought to mediate efferocytosis following tissue injury and thereby prevent excessive inflammation that could compromise tissue repair. To test this, we subjected mice lacking G2A or CD36 receptor to bleomycin-induced lung injury and measured efferocytosis, inflammation, and fibrosis. Loss of CD36 (but not G2A) delayed clearance of apoptotic alveolar cells (mean 78% increase in apoptotic cells 7 days postinjury), potentiated inflammation (mean 56% increase in lung neutrophils and 75% increase in lung KC levels 7 days postinjury, 51% increase in lung macrophages 14 days postinjury), and reduced lung fibrosis (mean 41% and 29% reduction 14 and 21 days postinjury, respectively). Reduced fibrosis in CD36(-/-) mice was associated with lower levels of profibrotic TH2 cytokines (IL-9, IL-13, IL-4), decreased expression of the M2 macrophage marker Arginase-1, and reduced interstitial myofibroblasts. G2A, on the other hand, was required for optimal clearance of apoptotic neutrophils during zymosan-induced peritoneal inflammation (50.3% increase in apoptotic neutrophils and 30.6% increase in total neutrophils 24 h following zymosan administration in G2A(-/-) mice). Thus, CD36 is required for timely removal of apoptotic cells in the context of lung injury and modulates subsequent inflammatory and fibrotic processes relevant to fibrotic lung disease.
authors: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors: Brian W
authors: BW
authors: Parks
authors: Leland L
authors: LL
authors: Black
authors: Kurt A
authors: KA
authors: Zimmerman
authors: Allison E
authors: AE
authors: Metz
authors: Chad
authors: C
authors: Steele
authors: Joanne E
authors: JE
authors: Murphy-Ullrich
authors: Janusz H
authors: JH
authors: Kabarowski
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001761:Bleomycin / Q000633:toxicity*; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D055370:Lung Injury / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D018955:CD36 Antigens; D018797:Cell Cycle Proteins; C115270:G2A receptor; D043562:Receptors, G-Protein-Coupled; D001761:Bleomycin
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