Silica-directed mast cell activation is enhanced by scavenger receptors

Jared M. Brown, Emily J. Swindle, Nataliya M. Kushnir-Sukhov, Andrij Holian, Dean D. Metcalfe

Research output: Contribution to journalArticlepeer-review

Abstract

Inhalation of crystalline silica results in pulmonary fibrosis and silicosis. It has been suggested that mast cells play a role in these conditions. How mast cells would influence pathology is unknown. We thus explored mast cell interactions with silica in vitro and in B6.Cg-Kit W-sh mast cell-deficient mice. B6.Cg-KitW-sh mice did not develop inflammation or significant collagen deposition after instillation of silica, while C57BI/6 wild-type mice did have these findings. Given this supporting evidence of a role for mast cells in the development of silicosis, we examined the ability of silica to activate mouse bone marrow-derived mast cells (BMMC), including degranulation (β-hexosaminidase release); production of reactive oxygen species (ROS) and inflammatory mediators; and the effects of silica on FcεRI-dependent activation. Silica did not induce mast cell degranulation. However, TNF-α, IL-13, monocyte chemotactic protein-1, protease activity, and production of ROS were dose-dependently increased after silica exposure, and production was enhanced after FcεRI stimulation. This mast cell activation was inhibited by anti-inflammatory compounds. As silica mediates some effects in macrophages through scavenger receptors (SRs), we first determined that mast cells express scavenger receptors; then explored the involvement of SR-A and macrophage receptor with colleagenous structure (MARCO). Silica-induced ROS formation, apoptosis, and TNF-α production were reduced in BMMC obtained from SR-A, MARCO, and SR-A/MARCO knockout mice. These findings demonstrate that silica directs mast cell production of inflammatory mediators, in part through SRs, providing insight into critical events in the pathogenesis and potential therapeutic targets in silicosis.

Original languageEnglish
Pages (from-to)43-52
Number of pages10
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume36
Issue number1
DOIs
StatePublished - Jan 2007

Keywords

  • B6.Cg-kit sash mouse
  • CD204
  • Macrophage receptor with collagenous structure
  • Mast cell
  • SR-A
  • Silicosis

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