Role of lysosomes in silica-induced inflammasome activation and inflammation in absence of MARCO.

ABSTRACT: MARCO is the predominant scavenger receptor for recognition and binding of silica particles by alveolar macrophages (AM). Previously, it was shown that mice null for MARCO have a greater inflammatory response to silica, but the mechanism was not described. The aim of this study was to determine the relationship between MARCO and NLRP3 inflammasome activity. Silica increased NLRP3 inflammasome activation and release of the proinflammatory cytokine, IL-1β, to a greater extent in MARCO(-/-) AM compared to wild type (WT) AM. Furthermore, in MARCO(-/-) AM there was greater cathepsin B release from phagolysosomes, Caspase-1 activation, and acid sphingomyelinase activity compared to WT AM, supporting the critical role played by lysosomal membrane permeabilization (LMP) in triggering silica-induce

SUBMITTER: Biswas R 

PROVIDER: S-EPMC4099041 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature