Proteinase-activated receptor-2 modulates human macrophage differentiation andeffector function

Steven, R., Crilly, A., Lockhart, J. C., Ferrell, W. R. and McInnes, I. B. (2013) Proteinase-activated receptor-2 modulates human macrophage differentiation andeffector function. Innate Immunity, 19(6), pp. 663-672. (doi: 10.1177/1753425913479984) (PMID:23606513)

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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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Steven, Miss Rachael and Ferrell, Professor William and Crilly, Dr Anne and Lockhart, Professor John
Authors: Steven, R., Crilly, A., Lockhart, J. C., Ferrell, W. R., and McInnes, I. B.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Innate Immunity
ISSN (Online):1753-4267
Copyright Holders:Copyright © 2013 The Authors
First Published:First published in Innate Immunity 19(6):663-672
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
337321PAR-2 as a novel therapeutic target in arthritisWilliam FerrellArthritis Research UK (ARC)L0559/14521III -IMMUNOLOGY