Abstract
In rodents, mast cell progenitors differentiate into distinct mucosal and serosal phenotypes which differ markedly in their functional responses to antigenic and peptidergic stimulation. Although the molecular basis of mast cell differentiation or functional specialization is unknown, it is possible that regulation of calcium entry contributes to one or both processes. The prolonged secretory response of mucosal mast cells (MMC) and the antigen-elicited synthesis of interleukin-3 by immature MMC both require a rise of cytoplasmic calcium sustained by Ca2+ influx across the plasma membrane. This Ca2+ entry is highly sensitive to membrane potential, affording a possible site for regulation of mast cell function by receptor-linked ion channels. We found that rat interleukin-3-dependent bone marrow-derived mast cells of the mucosal phenotype expressed two K+ conductances, neither of which is present in the prototype serosal mast cell from rat peritoneum. An inwardly rectifying K+ conductance was constitutively active and a latent outwardly rectifying K+ conductance was elicited rapidly upon ligation of cell surface adenosine or P2 purinergic receptors linked to G proteins of the Gi family. Stimulation of P2 receptors dramatically potentiated antigen-triggered secretion in a pertussis toxin-sensitive manner, suggesting that activation of the outwardly rectifying K+ channel may regulate antigen-dependent functions of MMC.
Highlights
mucosal mast cells (MMC) both require a rise of cytoplasmic calcium sus- histamine in response to several neuropeptide secretagogues tained by Ca” influx acrossthe plasma membrane
Cross-linkage of IgEreceptors on rodent IL-3-dependent mast cells stimulates them to prolifercells of the mucosal phenotypexpressedtwo K+conduc- ate and to synthesize and release IL-3, IL-4, and other cytotances, neither of which is present in the prototype se- kines implicated in themucosal immune response against helrosal mastcell from rat peritoneum.An inwardly recti- minths [10, 11]
During normalontogeny or as a consequence of antigen [19]. This outwardly rectifying K’ (K+oR)channel has parasitic infection these progenitors are recruited by various not been detected in numerous studiesof RPMC
Summary
MMC both require a rise of cytoplasmic calcium sus- histamine in response to several neuropeptide secretagogues tained by Ca” influx acrossthe plasma membrane This Ca2+entry is highly sensitive to membrane potential, affording a possiblseite for regulationof mast cell function by receptor-linked ion channels. During normalontogeny or as a consequence of antigen [19] This outwardly rectifying K’ (K+oR)channel has parasitic infection these progenitors are recruited by various not been detected in numerous studiesof RPMC Identification of the K+,Rand K+oRchannels in raBtMMC could provide a useful handle to explore the molecular basis of mast cell functional heterogeneity. "his work was presented in abstract form at the 1993 meeting of American Association of Immunologists [27]
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