Evidence for PI3K-dependent CXCR3 agonist-induced degranulation of human cord blood-derived mast cells

Molecular Immunology
Ian WilloxStephen G Ward

Abstract

The chemokine receptor CXCR3, which has three known variants (CXCR3-A, CXCR3-B and CXCR3-Alt), has been implicated in the recruitment of mast cells to tissues in many different chronic diseases with its agonists found in elevated levels in several pulmonary diseases. All three variants of CXCR3 were detected in cord blood-derived mast cells at the mRNA level. Using an antibody that is unable to distinguish individual CXCR3 isoforms, we detected a marked down-regulation of intracellular protein during maturation from progenitor cells, with no concomitant changes in the modest surface expression of CXCR3. The known CXCR3 agonists CXCL9, CXCL10 and CXCL11 as well as the reported CXCR3-B agonist CXCL4, were able to induce Akt and ERK1/2 phosphorylation, as well as partial degranulation. Responses to all agonists were inhibited by pre-treatment with selective CXCR3 antagonists and pertussis toxin. Use of novel isoform-selective inhibitors, indicates that the p110 gamma isoform of PI3K is required for degranulation and signaling responses to CXCR3 agonists.

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Citations

Jan 15, 2014·Journal of Molecular Neuroscience : MN·Dawei YeFeng Gao
Sep 28, 2013·Expert Opinion on Therapeutic Targets·Tej Pratap SinghJoshua M Farber
May 20, 2015·Biochimica Et Biophysica Acta·Benjamin M ManningChristy L Haynes
Nov 16, 2014·Journal of Cancer Research and Clinical Oncology·Huili LuAnja Moldenhauer
Mar 21, 2017·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·T KuroishiS Sugawara
May 15, 2018·Frontiers in Immunology·Heather L CaslinJohn J Ryan

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