Bazzoni G, Dejana E, Del Maschio A
Laboratory of Vascular Biology, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
Blood. 1991 May 1;77(9):2042-8.
The activation of polymorphonuclear leukocytes (PMN) is an important step in the development of tissue damage associated with inflammatory and ischemic conditions. Catecholamines have been reported to inhibit PMN functions, but the high concentrations required cast doubt on their actual relevance as a defense mechanism. We report here that adenosine, which is actively released in ischemic conditions, potentiates the effect of epinephrine and reduces the minimal active concentration required to inhibit PMN activation by at least two orders of magnitude. Epinephrine caused a dose-related reduction of chemiluminescence, superoxide anion generation, enzyme release (lysozyme and beta-glucuronidase), and adhesion to endothelial cell (EC) monolayers in human PMN activated by N-formyl-methionyl-leucyl-phenyl-alanine (fMLP). This effect was only apparent at 10(-7) to 10(-6) mol/L. As expected, adenosine caused dose-dependent reductions of superoxide anion production and PMN adhesion to EC. Adenosine and epinephrine combined had an additive effect on PMN superoxide production and adhesion to EC. The minimal effective concentration of epinephrine in combination with 10(-8) mol/L adenosine was in the range of 10(-10) to 10(-9) mol/L. In contrast, adenosine inhibited only slightly enzyme release and did not significantly enhance the inhibition by epinephrine on this parameter. Studies with adenosine analogs suggested that the potentiating effect of adenosine was mediated by A2 receptors. The mechanism of potentiation was not related to additive effect on intracellular cyclic adenosine monophosphate levels. Epinephrine's ability to modulate PMN activation and the potentiating effect of adenosine may constitute a form of physiologic protection against tissue injury in inflammatory and ischemic processes.
多形核白细胞（PMN）的激活是与炎症和缺血性疾病相关的组织损伤发展过程中的重要一步。据报道，儿茶酚胺可抑制PMN功能，但所需的高浓度使人怀疑其作为一种防御机制的实际相关性。我们在此报告，在缺血情况下会主动释放的腺苷可增强肾上腺素的作用，并将抑制PMN激活所需的最小有效浓度降低至少两个数量级。肾上腺素使由N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸（fMLP）激活的人PMN中的化学发光、超氧阴离子生成、酶释放（溶菌酶和β-葡萄糖醛酸酶）以及对内皮细胞（EC）单层的黏附呈剂量相关的降低。这种效应仅在10^(-7)至10^(-6) mol/L时明显。正如预期的那样，腺苷使超氧阴离子产生和PMN对EC的黏附呈剂量依赖性降低。腺苷和肾上腺素联合对PMN超氧产生和对EC的黏附具有相加作用。肾上腺素与10^(-8) mol/L腺苷联合的最小有效浓度在10^(-10)至10^(-9) mol/L范围内。相比之下，腺苷仅轻微抑制酶释放，且未显著增强肾上腺素对该参数的抑制作用。对腺苷类似物的研究表明，腺苷的增强作用是由A2受体介导的。增强机制与对细胞内环磷酸腺苷水平的相加作用无关。肾上腺素调节PMN激活的能力以及腺苷的增强作用可能构成炎症和缺血过程中针对组织损伤的一种生理保护形式。
