Proteinase-activated receptor-2 modulates human macrophage differentiation and effector function

Rachael Steven, Anne Crilly, John C Lockhart, William R. Ferrell, Iain B McInnes

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

Proteinase-activated receptor-2 (PAR-2) was shown to influence immune regulation; however, its role in human macrophage subset development and function has not been addressed. Here, PAR-2 expression and activation was investigated on granulocyte macrophage (GM)-CSF(M1) and macrophage (M)-CSF(M2) macrophages. In both macrophages, the PAR-2-activating peptide, SLIGKV, increased PAR-2 expression and regulated TNF-α and IL-10 secretion in a manner similar to LPS. In addition, HLA-DR on M1 cells also increased. Monocytes matured to an M1 phenotype in the presence of SLIGKV had reduced cell area, and released less TNF-α after LPS challenge compared with vehicle (P < 0.05, n = 3). Cells matured to an M2 phenotype with SLIGKV also had a reduced cell area and made significantly more TNF-α after LPS exposure compared to vehicle (P < 0.05, n = 3) with reduced IL-10 secretion (P < 0.05, n = 3). Thus, PAR-2 activation on macrophage subsets regulates HLA-DR and PAR-2 surface expression, and drives cytokine production. In contrast, PAR-2 activation during M1 or M2 maturation induces altered cell morphology and skewing of phenotype, as evidenced by cytokine secretion. These data suggest a complex role for PAR-2 in macrophage biology and may have implications for macrophage-driven disease in which proteinase-rich environments can influence the immune process directly.

Original languageEnglish
Pages (from-to)663-72
Number of pages10
JournalInnate Immunity
Volume19
Issue number6
DOIs
Publication statusPublished - Dec 2013

Keywords

  • Cell Differentiation
  • Cell Lineage
  • Cells, Cultured
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • HLA-DR Antigens
  • Humans
  • Interleukin-10
  • Lipopolysaccharides
  • Macrophage Activation
  • Macrophage Colony-Stimulating Factor
  • Macrophages
  • Oligopeptides
  • Receptor, PAR-2
  • Tumor Necrosis Factor-alpha
  • Up-Regulation

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