Gunther G R, Herring M B
Department of Surgery, Indiana University School of Medicine, Indianapolis 46202.
Ann Vasc Surg. 1991 Jul;5(4):325-30. doi: 10.1007/BF02015292.
To investigate the inhibitory effect of adenosine released by endothelium on neutrophil superoxide (O2-) production, we treated confluent monolayers of cultured human umbilical vein endothelial cells with the enzyme adenosine deaminase, and then added human neutrophils. Superoxide (O2-) production by human neutrophils stimulated with 10(-6) M formyl-methionyl-leucyl-phenylalanine was inhibited by 49% in the presence of a confluent monolayer of human umbilical vein endothelial cells (5.1 +/- 0.1 versus 2.6 +/- 0.3 nmols O2-/10(6) neutrophils). Addition of 0.25 U/ml adenosine deaminase to neutrophils plus endothelial cells restored formyl-methionyl-leucyl-phenylalanine-stimulated neutrophil superoxide production to the level seen with neutrophils alone. Deoxycoformycin (10(-4) M), an inhibitor of adenosine deaminase activity, prevented the increase in superoxide production associated with adenosine deaminase addition. The adenosine analogue 5'-(N-ethylcarboxamido)- adenosine (3 x 10(-4) M) caused increased inhibition of formyl-methionyl-leucylphenylalanine-stimulated superoxide release by neutrophils in the presence of endothelial cells and prevented neutrophil-mediated endothelial cell damage, as measured by release of 3H-2-deoxy-D-glucose. Pairing 2-chloroadenosine (10(-5) M) or 5'-(N-ethylcarboxamido)-adenosine (3 x 10(-4) M) with a cyclic adenosine monophosphate phosphodiesterase inhibitor, 3-isobutyl-l-methyl-xanthine (10-4 M), produced greater inhibition of neutrophil superoxide production than occurred with either compound alone. The results support the hypothesis that vascular endothelial cells protect themselves from neutrophil attack by releasing adenosine to inhibit superoxide production.
为研究内皮细胞释放的腺苷对中性粒细胞超氧化物（O2-）生成的抑制作用，我们用腺苷脱氨酶处理培养的人脐静脉内皮细胞融合单层，然后加入人中性粒细胞。在人脐静脉内皮细胞融合单层存在的情况下，用10(-6) M甲酰甲硫氨酰亮氨酰苯丙氨酸刺激的人中性粒细胞超氧化物（O2-）生成受到49%的抑制（5.1±0.1对2.6±0.3 nmol O2-/10(6)中性粒细胞）。向中性粒细胞加内皮细胞的体系中添加0.25 U/ml腺苷脱氨酶可使甲酰甲硫氨酰亮氨酰苯丙氨酸刺激的中性粒细胞超氧化物生成恢复到单独使用中性粒细胞时的水平。腺苷脱氨酶活性抑制剂脱氧助间型霉素（10(-4) M）可阻止与添加腺苷脱氨酶相关的超氧化物生成增加。腺苷类似物5'-（N-乙基羧酰胺基）-腺苷（3×10(-4) M）在有内皮细胞存在时可增强对甲酰甲硫氨酰亮氨酰苯丙氨酸刺激中性粒细胞释放超氧化物的抑制作用，并可防止中性粒细胞介导的内皮细胞损伤，这通过3H-2-脱氧-D-葡萄糖的释放来衡量。将2-氯腺苷（10(-5) M）或5'-（N-乙基羧酰胺基）-腺苷（3×10(-4) M）与环磷酸腺苷磷酸二酯酶抑制剂3-异丁基-1-甲基黄嘌呤（10-4 M）联合使用，对中性粒细胞超氧化物生成的抑制作用比单独使用任何一种化合物时都更强。这些结果支持以下假说：血管内皮细胞通过释放腺苷抑制超氧化物生成来保护自身免受中性粒细胞攻击。
