Mast cell subsets and their functional modulation by the Acanthocheilonema viteae product ES-62

Ball, D. H., Tay, H. K., Bell, K. S., Coates, M. L., Al-Riyami, L., Rzepecka, J., Harnett, W. and Harnett, M. M. (2013) Mast cell subsets and their functional modulation by the Acanthocheilonema viteae product ES-62. Journal of Parasitology Research, 2013, 961268. (doi: 10.1155/2013/961268)

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Publisher's URL: http://dx.doi.org/10.1155/2013/961268

Abstract

ES-62, an immunomodulator secreted by filarial nematodes, exhibits therapeutic potential in mouse models of allergic inflammation, at least in part by inducing the desensitisation of FcεRI-mediated mast cell responses. However, in addition to their pathogenic roles in allergic and autoimmune diseases, mast cells are important in fighting infection, wound healing, and resolving inflammation, reflecting that mast cells exhibit a phenotypic and functional plasticity. We have therefore characterised the differential functional responses to antigen (via FcεRI) and LPS and their modulation by ES-62 of the mature peritoneal-derived mast cells (PDMC; serosal) and those of the connective tissue-like mast cells (CTMC) and the mucosal-like mast cells derived from bone marrow progenitors (BMMC) as a first step to produce disease tissue-targeted therapeutics based on ES-62 action. All three mast cell populations were rendered hyporesponsive by ES-62 and whilst the mechanisms underlying such desensitisation have not been fully delineated, they reflect a downregulation of calcium and PKCα signalling. ES-62 also downregulated MyD88 and PKCδ in mucosal-type BMMC but not PDMC, the additional signals targeted in mucosal-type BMMC likely reflecting that these cells respond to antigen and LPS by degranulation and cytokine secretion whereas PDMC predominantly respond in a degranulation-based manner.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Harnett, Professor Margaret and Harnett, Professor William
Authors: Ball, D. H., Tay, H. K., Bell, K. S., Coates, M. L., Al-Riyami, L., Rzepecka, J., Harnett, W., and Harnett, M. M.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Journal of Parasitology Research
Publisher:Hindawi Publishing Corporation
ISSN:2090-0023
ISSN (Online):2090-0031
Copyright Holders:Copyright © 2013 The Authors
First Published:First published in Journal of Parasitology Research 2013L961268
Publisher Policy:Reproduced under a Creative Commons License

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