Autocrine production of cysteinyl leukotrienes activates human mast cells

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Proceedings titleJournal of Immunology
ConferenceAmerican Association of Immunologists Annual Meeting, May 2009, Seattle, WA
Pages139.13–; # of pages: 1
SubjectCysteinyl leukotrienes (CysLT); human mast cells; lipid mediators; cell degranulation
AbstractCysteinyl leukotrienes (CysLT) are potent inflammatory lipid mediators which are derived from 5-lipoxygenase activity. CysLTs mediate some of the pathophysiological responses associated with asthma such as bronchoconstriction, vasodilation and increased microvascular permeability, increased mucus secretion, decreased mucociliary clearance, eosinophil migration, and increased eosinophil survival. We now report that peripheral blood CD34+ progenitor-derived human mast cells and the human mast cell line (LAD2) express both CysLT receptors (CysLT1R and CysLT2R), the G protein-coupled receptors that bind CysLTs. LTC4, LTD4 and LTE4 activated LAD2 to produce MIP-1β and MCP-1 and production of these chemokines was inhibited by the CysLT1R inhibitor, monelukast. LAD2 activated by IgE/anti-IgE produced CysLT (980 + 55 pg/million cells) but LAD2 activated by substance P, a neuropeptide that also binds a G protein-coupled receptor, did not produce CysLT. Montelukast had no effect on SP-mediated LAD2 degranulation. CysLT did not induce human mast cell degranulation but montelukast inhibited FcRI-mediated human mast cell degranulation by approximately 20% suggesting that autocrine production of CysLT potentiated FcRI-dependent degranulation. IL-4 (10 ng/mL) in the presence of stem cell factor (SCF; 100 ng/mL) significantly upregulated expression of both CysLT1R and CysLT2R (16% and 32% respectively) and potentiated mast cell responses to LTE4 by up to 25%. Overall, these results show that human mast cell activation and degranulation is subject to autocrine CysLT-induced signaling which can be blocked by CysLT1R inhibitors such as montelukast.
Publication date
PublisherAmerican Association of Immunologists, Inc.
Copyright noticeMaterial in this document is covered by the provisions of the Copyright Act, by Canadian laws, policies, regulations and international agreements. Such provisions serve to identify the information source and, in specific instances, to prohibit reproduction of materials without written permission.
AffiliationNational Research Council Canada (NRC-CNRC); NRC Institute for Nutrisciences and Health
Access conditionavailable
Peer reviewedYes
NPARC number9345543
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Record identifierbdcfe475-10d4-405e-82d4-b5ae0e39f2af
Record created2009-10-03
Record modified2016-05-09
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