Zhong Hongyan, Shlykov Sergiy G, Molina Jose G, Sanborn Barbara M, Jacobson Marlene A, Tilley Stephen L, Blackburn Michael R
Department of Biochemistry and Molecular Biology, University of Texas-Houston Medical School, Houston, TX 77030, USA.
J Immunol. 2003 Jul 1;171(1):338-45. doi: 10.4049/jimmunol.171.1.338.
Adenosine has been implicated to play a role in asthma in part through its ability to influence mediator release from mast cells. Most physiological roles of adenosine are mediated through adenosine receptors; however, the mechanisms by which adenosine influences mediator release from lung mast cells are not understood. We established primary murine lung mast cell cultures and used real-time RT-PCR and immunofluorescence to demonstrate that the A(2A), A(2B), and A(3) adenosine receptors are expressed on murine lung mast cells. Studies using selective adenosine receptor agonists and antagonists suggested that activation of A(3) receptors could induce mast cell histamine release in association with increases in intracellular Ca(2+) that were mediated through G(i) and phosphoinositide 3-kinase signaling pathways. The function of A(3) receptors in vivo was tested by exposing mice to the A(3) receptor agonist, IB-MECA. Nebulized IB-MECA directly induced lung mast cell degranulation in wild-type mice while having no effect in A(3) receptor knockout mice. Furthermore, studies using adenosine deaminase knockout mice suggested that elevated endogenous adenosine induced lung mast cell degranulation by engaging A(3) receptors. These results demonstrate that the A(3) adenosine receptor plays an important role in adenosine-mediated murine lung mast cell degranulation.
腺苷被认为在哮喘中发挥作用，部分原因是它能够影响肥大细胞释放介质。腺苷的大多数生理作用是通过腺苷受体介导的；然而，腺苷影响肺肥大细胞释放介质的机制尚不清楚。我们建立了原代小鼠肺肥大细胞培养物，并使用实时逆转录聚合酶链反应和免疫荧光来证明A(2A)、A(2B)和A(3)腺苷受体在小鼠肺肥大细胞上表达。使用选择性腺苷受体激动剂和拮抗剂的研究表明，A(3)受体的激活可诱导肥大细胞组胺释放，并伴有通过G(i)和磷脂酰肌醇3-激酶信号通路介导的细胞内Ca(2+)增加。通过将小鼠暴露于A(3)受体激动剂IB-MECA来测试A(3)受体在体内的功能。雾化的IB-MECA直接诱导野生型小鼠肺肥大细胞脱颗粒，而对A(3)受体敲除小鼠没有影响。此外，使用腺苷脱氨酶敲除小鼠的研究表明，内源性腺苷升高通过激活A(3)受体诱导肺肥大细胞脱颗粒。这些结果表明，A(3)腺苷受体在腺苷介导的小鼠肺肥大细胞脱颗粒中起重要作用。
