The role of activated adenosine receptors in degranulation of human LAD2 mast cells.

Autor: Leung, Chi, Li, Ang, Banerjee, Juni, Gao, Zhan-Guo, Kambayashi, Taku, Jacobson, Kenneth, Civan, Mortimer
Zdroj: Purinergic Signalling; Sep2014, Vol. 10 Issue 3, p465-475, 11p
Abstrakt: Mast cell degranulation triggers hypersensitivity reactions at the body-environment interface. Adenosine modulates degranulation, but enhancement and inhibition have both been reported. Which of four adenosine receptors (ARs) mediate modulation, and how, remains uncertain. Also uncertain is whether adenosine reaches mast cell ARs by autocrine ATP release and ecto-enzymatic conversion. Uncertainties partly reflect species and cell heterogeneity, circumvented here by focusing on homogeneous human LAD2 cells. Quantitative PCR detected expression of A, A, and A, but not A, ARs. Nonselective activation of ARs with increasing NECA monotonically enhanced immunologically or C3a-stimulated degranulation. NECA alone stimulated degranulation slightly. Selective AR antagonists did not affect C3a-stimulated degranulation. NECA's enhancement of C3a-triggered degranulation was partially inhibited by separate application of each selective antagonist, and abolished by simultaneous addition of antagonists to the three ARs. Only the A antagonist separately inhibited NECA's enhancement of immunologically stimulated degranulation, which was abolished by simultaneous addition of the three selective antagonists. Immunological or C3a activation did not stimulate ATP release. NECA also enhanced immunologically triggered degranulation of mouse bone marrow derived mast cells (BMMCs), which was partially reduced only by simultaneous addition of the three antagonists or by the nonselective antagonist CGS15943. BMMCs also expressed A, A, and A ARs. but not AAR detectably. We conclude that (a) AAR is unnecessary for LAD2 degranulation or AR enhancement; (b) A, A, and A ARs all contribute to pharmacologic AR enhancement of LAD2 and BMMC degranulation; and (c) LAD2 cells depend on microenvironmental adenosine to trigger AR modulation. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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