PATHOGENESIS OF THE ADULT RESPIRATORY-DISTRESS SYNDROME - EVIDENCE OF OXIDANT ACTIVITY IN BRONCHOALVEOLAR LAVAGE FLUID
PATHOGENESIS OF THE ADULT RESPIRATORY-DISTRESS SYNDROME - EVIDENCE OF OXIDANT ACTIVITY IN BRONCHOALVEOLAR LAVAGE FLUID
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DOI：
10.1172/jci110823
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发表时间：
1983-01-01
影响因子：
15.9
通讯作者：
REVAK, SD
中科院分区：
文献类型：
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作者：
COCHRANE, CG;SPRAGG, R;REVAK, SD
有证据表明成人呼吸窘迫综合征(ARDS)患者的肺部会产生氧化剂。证据来自观察，在支气管肺泡灌洗(BAL)液中回收的α-1-PI[α-1-蛋白酶抑制物]已经被氧化失活，推测是氧化分子反应部位的甲硫基残基被氧化。α-1-PI的活性可以通过暴露于还原剂二硫苏糖醇和甲硫基亚砜多肽还原酶来恢复。恢复的活度与52,000[道尔顿]处存在的不活度α-1-PI的量成正比。52,000-Dα-1-PI的氧化也揭示了这一发现，当与猪胰腺弹性酶接触时，非活性分子被蛋白水解性切割到47,000 D，这是α-1-PI的特征，反应部位有氧化的甲硫基残基。体内α-1-PI的失活也是由于与一种活性酶(以前被证明是中性粒细胞弹性蛋白酶)的络合，以及体内产生47,000 mW片段的蛋白水解性切割所致。与BAL液相比，22例呼吸窘迫综合征患者血浆α-1-PI 90%活性14例，50-90%活性8例。显然，α-1-PI在离开血管进入肺后失活。呼吸窘迫综合征患者的循环α-1-PI与正常人的α-1-PI一样容易氧化失活。因此，患者不太可能因为不稳定的α-1-PI抑制剂而发生ARDS。
Evidence is presented indicating that oxidants are generated in lungs of patients with the adult respiratory distress syndrome (ARDS). The evidence was derived from observations that .alpha.-1-PI [.alpha.-1-proteinase inhibitor], recovered in bronchoalveolar lavage (BAL) fluid, had been inactivated by oxidation, presumably oxidation of the methionyl residue in the reaction site of the molecule. Activity of the .alpha.-1-PI could be restored by exposure to the reducing agent, dithiothreitol in the presence of methionyl sulfoxide peptide reductase. The amount of activity restored was proportional to the amount of inactive .alpha.-1-PI present at 52,000 D [daltons]. Oxidation of the 52,000-D .alpha.-1-PI was also revealed by the finding that the inactive molecule was subject to proteolytic cleavage to 47,000 D when exposed to porcine pancreatic elastase, a characteristic of .alpha.-1-PI with oxidized methionyl residues in the reactive site. Inactivation of the .alpha.-1-PI in vivo also resulted from complexing to an active enzyme, shown previously to be neutrophil elastase, and from proteolytic cleavage in vivo, that produced a fragment of 47,000 MW. In contrast to that in BAL fluids, the .alpha.-1-PI in plasma of patients with respiratory distress syndrome was > 90% active in 14 of 22 cases and 50-90% active in 8 cases. Evidently, .alpha.-1-PI was inactivated after leaving the vessels and entering the lung. The circulating .alpha.-1-PI in patients with the respiratory distress syndrome was equally susceptible to oxidative inactivation as .alpha.-1-PI from normal individuals. It seems improbable therefore that patients develop ARDS because of labile .alpha.-1-PI inhibitor.