Document Type

Article

Publication Title

Journal of Immunology Research

Publisher

Hindawi Publishing Corporation

Publication Date

6-26-2014

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-1b, 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 toWT AM, supporting the critical role played by lysosomal membrane permeabilization (LMP) in triggering silica-induced inflammation.The difference in sensitivity to LMP appears to be in cholesterol recycling since increasing cholesterol in AM by treatment with U18666A decreased silica-induced NLRP3 inflammasome activation, and cells lacking MARCO were less able to sequester cholesterol following silica treatment. Taken together, these results demonstrate thatMARCO contributes to normal cholesterol uptake in macrophages; therefore, in the absence ofMARCO, macrophages are more susceptible to a greater inflammatory response by particulates known to cause NLRP3 inflammasome activation and the effect is due to increased LMP.

DOI

10.1155/2014/304180

Rights

© 2014 Rupa Biswas et al.

Creative Commons License

Creative Commons Attribution 3.0 License
This work is licensed under a Creative Commons Attribution 3.0 License.

Included in

Public Health Commons

Share

COinS