Neutrophil adherence to endothelium is enhanced via adenosine A1 receptors and inhibited via adenosine A2 receptors.
Neutrophil adherence to endothelium is enhanced via adenosine A1 receptors and inhibited via adenosine A2 receptors.
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DOI：
10.4049/jimmunol.148.7.2201
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发表时间：
1992-04
影响因子：
4.4
通讯作者：
B. Cronstein;R. Levin;M. Philips;R. Hirschhorn;S. Abramson;G. Weissmann
中科院分区：
文献类型：
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作者：
B. Cronstein;R. Levin;M. Philips;R. Hirschhorn;S. Abramson;G. Weissmann
我们最近已经证明，人中性粒细胞（PMN）具有两种不同类型的腺苷受体（A1和A2），当被占据时，促进趋化性并抑制活性氧的产生（例如，O2-和H2 O2）。我们以前已经证明，腺苷保护内皮细胞（EC）的损伤刺激中性粒细胞（PMN）通过减少产生的H2 O2和抑制粘附的PMN EC。因此，我们确定是否占用A1或A2腺苷受体调节粘附的中性粒细胞EC。在类似于通过连接A2受体来抑制O2-释放所需的浓度下，腺苷（IC 50 = 56 nM）和5 'N-乙基羧酰胺腺苷（NECA，IC 50 = 8 nM）（最有效的A2激动剂）都能抑制受刺激的PMN（FMLP，0.1 μ M）对EC的粘附。与此相反，特异性A1激动剂N6-苯基异丙基腺苷和N6-环戊基腺苷（CPA）在1-100 nM浓度下促进PMN粘附EC。为了进一步研究腺苷受体激动剂影响受刺激PMN粘附的机制，我们检测了NECA（A2）和CPA（A1）对PMN与纤维蛋白原（β 2整合素CD 11b/CD 18的配体）和明胶粘附的影响。NECA以剂量依赖性方式（IC 50 = 2 nM）抑制FMLP处理的PMN与纤维蛋白原包被板的粘附，但不抑制明胶包被板的粘附。相比之下，CPA（A1）促进受刺激的PMN粘附明胶-（EC 50 = 13 pM），但不是纤维蛋白原包被的板。茶碱（10 μ M），腺苷受体拮抗剂，逆转抑制NECA（0.3 μ M）的刺激中性粒细胞粘附纤维蛋白原。这些观察结果不仅证实了PMN上存在A1和A2受体，而且还表明腺苷在炎症中的两种相反作用。A1受体的占据促进中性粒细胞粘附于内皮和趋化性（促炎作用），而A2受体的占据抑制粘附和有毒氧代谢产物的产生（促炎作用）。
We have recently demonstrated that human neutrophils (PMN) possess two different classes of adenosine receptors (A1 and A2) that, when occupied, promote chemotaxis and inhibit the generation of reactive oxygen species (e.g., O2- and H2O2), respectively. We have previously demonstrated that adenosine protects endothelial cells (EC) from injury by stimulated neutrophils (PMN) both by diminishing generation of H2O2 and inhibiting adherence of PMN to EC. We therefore determined whether occupancy of A1 or A2 adenosine receptors regulated adherence of PMN to EC. At concentrations similar to those required to inhibit release of O2- by ligation of A2 receptors, both adenosine (IC50 = 56 nM) and 5'N-ethylcarboxamidoadenosine (NECA, IC50 = 8 nM), the most potent A2 agonist, inhibited adherence to EC by stimulated PMN (FMLP, 0.1 microM). In direct contrast, the specific A1 agonists N6-phenylisopropyladenosine and N6-cyclopentyladenosine (CPA) promoted PMN adherence to EC at concentrations of 1-100 nM. To further investigate the mechanisms by which adenosine receptor agonists affected the adherence of stimulated PMN we examined the effect of NECA (A2) and CPA (A1) on the adherence of PMN to fibrinogen (a ligand for the beta 2 integrin CD11b/CD18) and to gelatin. In a dose-dependent manner (IC50 = 2 nM), NECA inhibited the adherence of FMLP-treated PMN to fibrinogen- but not gelatin-coated plates. In contrast, CPA (A1) promoted adherence of stimulated PMN to gelatin-(EC50 = 13 pM) but not fibrinogen-coated plates. Theophylline (10 microM), an adenosine receptor antagonist, reversed the inhibition by NECA (0.3 microM) of stimulated neutrophil adherence to fibrinogen. These observations not only confirm the presence of A1 and A2 receptors on PMN but also suggest two opposing roles for adenosine in inflammation. Occupancy of A1 receptors promotes neutrophil adherence to endothelium and chemotaxis (a proinflammatory role) whereas occupancy of A2 receptors inhibits adherence and generation of toxic oxygen metabolites (an antiinflammatory role).