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中性粒细胞弹性蛋白酶-α1-蛋白酶抑制剂相互作用的氧化调节

Oxidative regulation of neutrophil elastase-alpha-1-proteinase inhibitor interactions.

作者信息

Ossanna P J, Test S T, Matheson N R, Regiani S, Weiss S J

出版信息

J Clin Invest. 1986 Jun;77(6):1939-51. doi: 10.1172/JCI112523.

DOI:10.1172/JCI112523
PMID:3519684
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC370555/
Abstract

Triggered human neutrophils were able to maintain released elastase in an active form in the presence of purified alpha-1-proteinase inhibitor (alpha-1-PI), serum or bronchoalveolar lavage fluid (BAL). The accumulation of free elastase activity was associated with a decrease in the ability of the alpha-1-PI to inhibit porcine pancreatic elastase, an increase in proteinase activity associated with alpha-2-macroglobulin, and the oxidation of alpha-1-PI to a molecule containing four methionine sulfoxide residues. Neutrophils used both hypochlorous acid and long-lived N-chloroamines to oxidize the alpha-1-PI, but hypochlorous acid was preferentially used for suppressing the activity of the antiproteinase over short distances whereas the N-chloroamines were effective even when the phagocytes and alpha-1-PI were physically separated. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of purified alpha-1-PI, serum, or BAL that had been incubated with triggered neutrophils revealed that the released neutrophil elastase was not complexed with the antiproteinase and that a portion of the alpha-1-PI had undergone proteolysis. These data suggest that the presence of free neutrophil elastase as well as inactive, oxidized, and proteolyzed alpha-1-PI in fluids recovered from inflammatory sites in vivo could be directly mediated by triggered neutrophils alone.

摘要

在纯化的α-1-蛋白酶抑制剂(α-1-PI)、血清或支气管肺泡灌洗液(BAL)存在的情况下,被激活的人类中性粒细胞能够使释放的弹性蛋白酶保持活性形式。游离弹性蛋白酶活性的积累与α-1-PI抑制猪胰弹性蛋白酶能力的降低、与α-2-巨球蛋白相关的蛋白酶活性增加以及α-1-PI氧化为含有四个甲硫氨酸亚砜残基的分子有关。中性粒细胞使用次氯酸和长寿命的N-氯胺来氧化α-1-PI,但次氯酸优先用于在短距离内抑制抗蛋白酶的活性,而即使吞噬细胞和α-1-PI在物理上分离,N-氯胺也有效。对与被激活的中性粒细胞孵育后的纯化α-1-PI、血清或BAL进行十二烷基硫酸钠-聚丙烯酰胺凝胶电泳显示,释放的中性粒细胞弹性蛋白酶未与抗蛋白酶形成复合物,且一部分α-1-PI发生了蛋白水解。这些数据表明,体内炎症部位回收的液体中游离中性粒细胞弹性蛋白酶以及无活性、氧化和蛋白水解的α-1-PI的存在可能仅由被激活的中性粒细胞直接介导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48d6/370555/de127f625f44/jcinvest00711-0226-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48d6/370555/d5eaf5a5a3ea/jcinvest00711-0223-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48d6/370555/31a4f143aa55/jcinvest00711-0225-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48d6/370555/de127f625f44/jcinvest00711-0226-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48d6/370555/d5eaf5a5a3ea/jcinvest00711-0223-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48d6/370555/31a4f143aa55/jcinvest00711-0225-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48d6/370555/de127f625f44/jcinvest00711-0226-a.jpg

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