Felsch A, Stöcker K, Borchard U
Institute for Pharmacology, Heinrich-Heine-Universität at Düsseldorf, Germany.
J Immunol. 1995 Jul 1;155(1):333-8.
In this study we investigated the effect of adenosine receptor agonists on the adherence of PMA-stimulated human neutrophils to cultured porcine aortic endothelial cells. Additionally, we studied the influence of adenosine analogues on the second messenger cAMP in neutrophils and cultured endothelial cells. In the presence of 10 ng/ml PMA, there was a rapid and stable increase on adherence of neutrophils to the endothelial layer. The adenosine A2 receptor agonists, 2-(p-(2-carboxylethyl)phenethylamino)-5' N-ethylcarboxamido-adenosine (CGS 21680) (0.01 to 1 microM) and 5' N-ethylcarboxamidoadenosine (NECA) (0.01 to 1 microM) decreased the adherence of PMA-stimulated neutrophils maximally by 43% and 34%, respectively. In contrast the adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (0.01 to 1 microM) showed a 30% increase in PMA-stimulated adherence of neutrophils to endothelial cells. CGS 21680 (0.01 to 1 microM) and NECA (0.01 to 1 microM) were without detectable effect on the formation of cAMP in neutrophils and endothelial cells; however, in the presence of the phosphodiesterase inhibitor Ro 20-1724 (70 microM), CGS 21680 and NECA maximally increased cAMP level 20-fold and 10-fold, respectively, in neutrophils, and 1.8-fold and 2-fold, respectively, in cultured endothelial cells. However, addition of 70 microM Ro 20-1724 to the adherence assay did not potentiate the inhibitory effects of CGS 21680 and NECA on PMA-stimulated neutrophil adherence. On the other hand, 2-chloro-N6-cyclopentyladenosine (0.01 to 1 microM) did not significantly alter cAMP level in neutrophils and endothelial cells in the presence of 4(3-butoxy-4-methoxyphenyl)methyl)-2-imidazolidinone (Ro 20-1724). Our results indicate that adenosine A2 receptor agonists decrease phorbol ester-stimulated adherence of neutrophils to cultured endothelial cells. This effect is possibly independent of adenosine A2 receptor-mediated stimulation of adenylate cyclase in neutrophils and cultured endothelial cells.
在本研究中，我们调查了腺苷受体激动剂对佛波酯（PMA）刺激的人中性粒细胞与培养的猪主动脉内皮细胞黏附的影响。此外，我们研究了腺苷类似物对中性粒细胞和培养的内皮细胞中第二信使环磷酸腺苷（cAMP）的影响。在存在10 ng/ml PMA的情况下，中性粒细胞与内皮层的黏附迅速且稳定地增加。腺苷A2受体激动剂2-(对-(2-羧乙基)苯乙氨基)-5'-N-乙基羧酰胺基腺苷（CGS 21680）（0.01至1 microM）和5'-N-乙基羧酰胺基腺苷（NECA）（0.01至1 microM）分别使PMA刺激的中性粒细胞黏附最大程度降低了43%和34%。相比之下，腺苷A1受体激动剂2-氯-N6-环戊基腺苷（0.01至1 microM）使PMA刺激的中性粒细胞与内皮细胞的黏附增加了30%。CGS 21680（0.01至1 microM）和NECA（0.01至1 microM）对中性粒细胞和内皮细胞中cAMP的形成无明显影响；然而，在磷酸二酯酶抑制剂Ro 20-1724（70 microM）存在的情况下，CGS 21680和NECA分别使中性粒细胞中的cAMP水平最大增加20倍和10倍，在培养的内皮细胞中分别增加1.8倍和2倍。然而，在黏附试验中加入70 microM Ro 20-1724并未增强CGS 21680和NECA对PMA刺激的中性粒细胞黏附的抑制作用。另一方面，在存在4(3-丁氧基-4-甲氧基苯基)甲基)-2-咪唑啉酮（Ro 20-1724）的情况下，2-氯-N6-环戊基腺苷（0.01至1 microM）对中性粒细胞和内皮细胞中的cAMP水平无显著影响。我们的结果表明，腺苷A2受体激动剂可降低佛波酯刺激的中性粒细胞与培养的内皮细胞的黏附。这种作用可能独立于腺苷A2受体介导的中性粒细胞和培养的内皮细胞中腺苷酸环化酶的刺激。
