Fc gamma receptor-mediated functions in neutrophils are modulated by adenosine receptor occupancy. A1 receptors are stimulatory and A2 receptors are inhibitory.
Fc gamma receptor-mediated functions in neutrophils are modulated by adenosine receptor occupancy. A1 receptors are stimulatory and A2 receptors are inhibitory.
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DOI：
10.4049/jimmunol.145.7.2235
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发表时间：
1990-10
影响因子：
4.4
通讯作者：
J. E. Salmon;B. Cronstein
中科院分区：
文献类型：
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作者：
J. E. Salmon;B. Cronstein
腺苷是一种内源性释放的嘌呤，通过表面A1和A2受体调节许多细胞的功能。我们研究了腺苷受体连接调节Fc γ R触发的多形核白细胞（PMN）的炎症反应的假设，这是一种免疫复合物疾病的发病机制至关重要的反应。研究了腺苷类似物对人中性粒细胞中Fc γ R介导的吞噬作用和超氧阴离子（O2-）产生的影响。最有效的A2受体激动剂5 '（N-乙基）羧酰胺腺苷（NECA）抑制Fc γ R介导的吞噬作用和O2-产生，而高度选择性的A1受体激动剂N6-环戊基腺苷（CPA）增强这些功能。腺苷类似物的作用在粘附于生物表面的中性粒细胞中显著增强。NECA的抑制和CPA对PMN Fc γ R功能的增强均被腺苷受体拮抗剂8-对磺苯基茶碱阻断，这表明表面腺苷受体的占据介导了这些类似物的作用。由于PMN上的A1受体与百日咳毒素敏感的G蛋白有关，我们的证据表明百日咳毒素阻断了CPA而不是NECA对Fc γ R功能的影响，这进一步支持了CPA通过A1受体起作用的假设。我们的数据表明，腺苷A1和A2受体以相反的方式调节中性粒细胞Fc γ R功能，从而形成浓度依赖性、腺苷调节的反馈回路。在低浓度下，通过PMN A1受体增强中性粒细胞Fc γ R功能，而在较高浓度下（可能发生在受损组织部位），通过A2受体抑制。我们观察到腺苷类似物对粘附的中性粒细胞具有更有效的作用，这强调了腺苷作为体内Fc γ R触发的炎症的调节剂的潜在重要性。
Adenosine, an endogenously released purine, modulates the functions of many cells through surface A1 and A2 receptors. We examined the hypothesis that adenosine receptor ligation regulates Fc gamma R-triggered inflammatory response by polymorphonuclear leukocytes (PMN), a response which is critical to the pathogenesis of immune complex diseases. The effects of adenosine analogs on Fc gamma R-mediated phagocytosis and superoxide anion (O2-) generation in human neutrophils were investigated. 5'(N-ethyl)carboxamidoadenosine (NECA), the most potent A2 receptor agonist, inhibited Fc gamma R-mediated phagocytosis and O2- generation, whereas N6-cyclopentyladenosine (CPA), a highly selective A1 receptor agonist, enhanced these functions. The effects of the adenosine analogs were markedly accentuated in neutrophils adherent to biologic surfaces. Both the inhibition by NECA and the enhancement by CPA of PMN Fc gamma R functions were blocked by the adenosine receptor antagonist 8-p-sulfophenyltheophylline, which suggests that occupancy of surface adenosine receptors mediated the actions of these analogs. Because A1 receptors on PMN are linked to pertussis toxin-sensitive G proteins, our evidence that pertussis toxin blocked the effects on Fc gamma R function brought about by CPA but not by NECA further supports the hypothesis that CPA acts via an A1 receptor. Our data indicate that adenosine A1 and A2 receptors modulate neutrophil Fc gamma R function in opposing ways, allowing for a concentration-dependent, adenosine-regulated feed-back loop. At low concentrations there is enhancement of neutrophil Fc gamma R function via PMN A1 receptors, whereas at higher concentrations (those which may occur at sites of damaged tissues), there is inhibition via A2 receptors. Our observation that adenosine analogs had more potent effects on adherent neutrophils emphasizes the potential importance of adenosine as a modulator of Fc gamma R-triggered inflammation in vivo.