Alpha 1 antitrypsin and protease complexation is induced by lipopolysaccharide, interleukin-1β, and tumor necrosis factor-α in monocytes
Alpha 1 antitrypsin and protease complexation is induced by lipopolysaccharide, interleukin-1β, and tumor necrosis factor-α in monocytes
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DOI：
10.1164/ajrccm.157.1.9702033
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发表时间：
1998-01-01
影响因子：
24.7
通讯作者：
Wewers, MD
中科院分区：
文献类型：
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作者：
Knoell, DL;Ralston, DR;Wewers, MD
α 1-抗胰蛋白酶（α 1-AT）的局部调控可能对炎症细胞微环境中蛋白酶-抗蛋白酶平衡的维持具有重要意义。因此，我们研究了脂多糖（LPS）、白细胞介素-1 β (IL-1 β)和肿瘤坏死因子- α (TNF α)是否影响人外周血单核细胞（PBMC）中α 1-AT的细胞周浓度。取正常健康志愿者的PBMC，用LPS、IL-1 β和TNF α处理，并测量条件上清中人α 1-AT的浓度。与未受刺激的对照上清液（147 +/- 19 ng/ml）相比，LPS （439 +/- 66 ng/ml， p小于或等于0.001）、IL-1 β （263 +/- 37 ng/ml， p小于或等于0.01）和TNF α （316 +/- 59 ng/ml， p小于或等于0.05）诱导α 1-AT增加2- 3倍。α 1-AT蛋白的上调与α 1-AT mRNA的增加相关，表明α 1-AT合成同时增加。尽管α 1-AT浓度升高，但未检测到功能性抗蛋白酶活性。此外，所有样品中都存在蛋白酶活性，其活性与上清中测量的α 1-AT的量呈负相关。这些发现表明，局部炎症条件上调单核细胞α 1-AT的产生，单核细胞与来自PBMC群体的蛋白酶结合。
Local regulation of alpha 1-antitrypsin (alpha 1-AT) may have importance in maintenance of the protease-antiprotease balance in the microenvironment of inflammatory cells. We therefore studied whether lipopolysaccharide (LPS), interleukin-1 beta (IL-1 beta), and tumor necrosis factor-alpha (TNF alpha) affect the pericellular concentration of alpha 1-AT in human peripheral blood mononuclear cells (PBMC). PBMC taken from normal healthy volunteers were treated with LPS, IL-1 beta, and TNF alpha, and the concentration of human alpha 1-AT in conditioned supernatants was measured. When compared with unstimulated control supernatants (147 +/- 19 ng/ml), LPS (439 +/- 66 ng/ml; p less than or equal to 0.001), IL-1 beta (263 +/- 37 ng/ml; p less than or equal to 0.01), and TNF alpha (316 +/- 59 ng/ml; p less than or equal to 0.05) induced a 2- to 3-fold increase of alpha 1-AT. Up-regulation of alpha 1-AT protein correlated with an increase in alpha 1-AT mRNA, suggesting a simultaneous increase in alpha 1-AT synthesis. Despite the increase in alpha 1-AT concentration, functional antiprotease activity could not be detected. Furthermore, protease activity was present in all samples, with the amount of activity being inversely related to the amount of alpha 1-AT measured in supernatants. These findings suggest that local inflammatory conditions up-regulate alpha 1-AT production by monocytes which complex with a protease derived from the PBMC population.