Secretory leukocyte proteinase inhibitor is a major leukocyte elastase inhibitor in human neutrophils

Secretory leukocyte proteinase inhibitor is a major leukocyte elastase inhibitor in human neutrophils
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DOI:
10.1002/jlb.61.6.695
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发表时间:
1997-06-01
影响因子:
5.5
通讯作者:
Gauldie, J
Gauldie, J
中科院分区:
医学3区
文献类型:
--
作者:
Sallenave, JM;Si-Tahar, M;Gauldie, J

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分泌性白细胞蛋白酶抑制剂(SLPI)是肺部炎症期间上呼吸道中发现的主要中性粒细胞弹性蛋白酶(HLE)抑制剂,已显示其在体外由上皮细胞合成和分泌,并通过免疫细胞化学定位于气管腺体和细支气管上皮细胞。在本研究中,使用特异性抗SLPI免疫球蛋白G(IgG)的免疫检测和免疫纯化技术,我们证明SLPI作为一种中性粒细胞胞质中的天然 14-kDa 分子。此外,我们证明 SLPI 是中性粒细胞胞质中存在的 HLE 的主要抑制剂,因为与特异性抗 SLPI IgG 预孵育能够完全抑制胞质溶胶的抗 HLE 活性,SLPI 可以由中性粒细胞分泌(可能以非活性形式),并且当用佛波醇肉豆蔻酸酯乙酸酯 (PMA) 刺激细胞时,其分泌会增强。 Elafin 是一种弹性蛋白酶特异性抑制剂,也以微量存在于中性粒细胞胞质中,并且其分泌可以上调。中性粒细胞胞质中 SLPI 的存在可以作为针对从嗜天青颗粒溢出的蛋白酶的保护屏障。替代或补充作用可能是维持分化的表型。
Secretory leukocyte proteinase inhibitor (SLPI) is the main neutrophil elastase (HLE) inhibitor found in the upper airways during pulmonary inflammation, It has been shown to be synthesized and secreted in vitro by epithelial cells and has been localized in tracheal glands and bronchiolar epithelial cells by immunocytochemistry, In this study, using immunodetection and immunopurification techniques with specific anti-SLPI immunoglobulin G (IgG), we show that SLPI is present as a native 14-kDa molecule in neutrophil cytosol. In addition, we demonstrate that SLPI is the major inhibitor of HLE present in neutrophil cytosol because pre-incubation with specific anti-SLPI IgG was able to inhibit completely the anti-HLE activity of the cytosol, SLPI can be secreted (probably in an inactive form) by neutrophils and its secretion is enhanced when the cells are stimulated with phorbol myristate acetate (PMA)). Elafin, an elastase-specific inhibitor, is also present in minute amounts in neutrophil cytosol and its secretion can be up-regulated, The presence of SLPI in the cytosol of neutrophils may serve as a protective screen against proteinases spilling from azurophilic granules, An alternative or supplementary role may be the maintenance of a differentiated phenotype.