Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/14950
Title: Engagement of the EP2 prostanoid receptor closes the K+ channel KCa3.1 in human lung mast cells and attenuates their migration.
Authors: Duffy, SM
Cruse, G
Cockerill, SL
Brightling, CE
Bradding, P
First Published: Sep-2008
Citation: EUR J IMMUNOL, 2008, 38 (9), pp. 2548-2556
Abstract: Human lung mast cells (HLMC) express the Ca(2+)-activated K(+) channel K(Ca)3.1, which plays a crucial role in their migration to a variety of diverse chemotactic stimuli. K(Ca)3.1 activation is attenuated by the beta(2)-adrenoceptor and the adenosine A(2A) receptor through a G(s)-coupled mechanism independent of cyclic AMP. Prostaglandin E(2) promotes degranulation and migration of mouse bone marrow-derived mast cells through the G(i)-coupled EP(3) prostanoid receptor, and induces LTC(4) and cytokine secretion from human cord blood-derived mast cells. However, PGE(2) binding to the G(s)-coupled EP(2) receptor on HLMC inhibits their degranulation. We show that EP(2) receptor engagement closes K(Ca)3.1 in HLMC. The EP(2) receptor-specific agonist butaprost was more potent than PGE(2) in this respect, and the effects of both agonists were reversed by the EP(2) receptor antagonist AH6809. Butaprost markedly inhibited HLMC migration induced by chemokine-rich airway smooth muscle-conditioned media. Interestingly, PGE(2) alone was chemotactic for HLMC at high concentrations (1 microM), but was a more potent chemoattractant for HLMC following EP(2) receptor blockade. Therefore, the G(s)-coupled EP(2) receptor closes K(Ca)3.1 in HLMC and attenuates both chemokine- and PGE(2)-dependent HLMC migration. EP(2) receptor agonists with K(Ca)3.1 modulating function may be useful for the treatment of mast cell-mediated disease.
DOI Link: 10.1002/eji.200738106
ISSN: 0014-2980
Links: http://hdl.handle.net/2381/14950
Type: Journal Article
Appears in Collections:Published Articles, Dept. of Infection, Immunity and Inflammation

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