ADENOSINE - AN ENDOGENOUS INHIBITOR OF NEUTROPHIL-MEDIATED INJURY TO ENDOTHELIAL-CELLS
ADENOSINE - AN ENDOGENOUS INHIBITOR OF NEUTROPHIL-MEDIATED INJURY TO ENDOTHELIAL-CELLS
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DOI：
10.1172/jci112638
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发表时间：
1986-09-01
影响因子：
15.9
通讯作者：
HIRSCHHORN, R
中科院分区：
文献类型：
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作者：
CRONSTEIN, BN;LEVIN, RI;HIRSCHHORN, R
由于腺苷及其类似物2-氯腺苷防止中性粒细胞产生超氧阴离子的化学引诱剂，我们试图确定这些药物是否可以抑制嗜中性粒细胞介导的内皮细胞损伤。化学引诱物N-甲酰基-甲硫氨酰基-亮氨酰基-苯丙氨酸（FMLP，0.1 μ M）使中性粒细胞对内皮细胞的粘附增强两倍（18 ± 10 μ M）。2% vs. 39 .+-. 3%粘附，P < 0.001），并对内皮细胞造成实质性的嗜酸性粒细胞介导的损伤（2 . ±. 2% vs. 39 .+-. 4%细胞毒性，P < 0.001）。2-氯腺苷（10 μ M）不仅抑制了60%（24 ± 0.5%）的受刺激中性粒细胞的粘附，2%粘附，P < 0.001），但也使细胞毒性降低了51%（20 . ±. 4%细胞毒性，P < 0.002）。此外，通过腺苷脱氨酶从培养基中消耗内源性释放的腺苷增强了刺激的中性粒细胞对内皮细胞的损伤（从39 ± 10 μ g/ml）。4%至69 .+-。3%细胞毒性，P < 0.001）。事实上，在腺苷脱氨酶存在的情况下，甚至未受刺激的嗜中性粒细胞也会损伤内皮细胞（19 . ±. 4% vs. 2 .+-. 2%细胞毒性，P < 0.001）。这些数据表明，腺苷受体的参与防止中性粒细胞的粘附和它们对内皮细胞造成的损伤。腺苷不仅抑制由化学引诱物刺激的细胞引起的损伤，而且抑制未刺激的细胞引起的损伤。基于这种急性血管损伤模型，我们认为腺苷不仅是一种有效的血管扩张剂，而且还具有保护血管内皮免受中性粒细胞损伤的作用。
Since adenosine and its analogue 2-chloroadenosine prevent neutrophils from generating superoxide anion in response to chemoattractants, we sought to determine whether these agents could inhibit neutrophil-mediated injury of endothelial cells. The chemoattractant N-formyl-methionyl-leucyl-phenylalanine (FMLP, 0.1 .mu.M) enhanced the adherence of neutrophils to endothelial cells twofold (18 .+-. 2% vs. 39 .+-. 3% adherence, P < 0.001) and caused substantial neutrophil-mediated injury to endothelial cells (2 .+-. 2% vs. 39 .+-. 4% cytotoxicity, P < 0.001). 2-Chloroadenosine (10 .mu.M) not only inhibited the adherence of stimulated neutrophils by 60% (24 .+-. 2% adherence, P < 0.001) but also diminished the cytotoxicity by 51% (20 .+-. 4% cytotoxicity, P < 0.002). Furthermore, depletion of endogenously released adenosine from the medium by adenosine deaminase-enhanced injury to endothelial cells by stimulated neutrophils (from 39 .+-. 4% to 69 .+-. 3% cytotoxicity, P < 0.001). Indeed, in the presence of adenosine deaminase, even unstimulated neutrophils injured endothelial cells (19 .+-. 4% vs. 2 .+-. 2% cytotoxicity, P < 0.001). These data indicate that engagement of adenosine receptors prevents both the adhesion of neutrophils and the injury they cause to endothelial cells. Adenosine inhibits injury provoked not only by cells that have been stimulated by chemoattractants but also by unstimulated cells. Based on this model of acute vascular damage we suggest that adenosine is not only a potent vasodilator, but plays the additional role of protecting vascular endothelium from damage by neutrophils.