Alternative activation of macrophages and pulmonary fibrosis are modulated by scavenger receptor, macrophage receptor with collagenous structure

摘要: Alternative activation of alveolar macrophages is linked to fibrosis following exposure asbestos. The scavenger receptor, macrophage receptor with collagenous structure (MARCO), provides innate immune defense against inhaled particles and pathogens; however, a for asbestos has not been identified. We hypothesized that MARCO acts as an initial signaling asbestos, polarizes profibrotic M2 phenotype, required the development asbestos-induced fibrosis. Compared normal subjects, isolated from patients asbestosis express higher amounts have greater polarization. Arginase 1 (40-fold) IL-10 (265-fold) were in patients. In vivo, genetic deletion attenuated environment pulmonary mice exposed chrysotile. Moreover, MARCO(-/-) polarize M1 whereas wild-type Ym1 (>3.0-fold) nearly 7-fold more active TGF-β1 bronchoalveolar lavage (BAL) fluid (BALF). Arg(432) Arg(434) domain V are polarization phenotype mutation these residues reduced FIZZ1 expression (17-fold) compared cells expressing MARCO. These observations demonstrate membrane protein regulates fibrotic response lung injury suggest novel target therapeutic intervention.