Direct cytotoxicity of polymorphonuclear leukocyte granule proteins to human lung-derived cells and endothelial cells.
Direct cytotoxicity of polymorphonuclear leukocyte granule proteins to human lung-derived cells and endothelial cells.
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多形核白细胞颗粒蛋白对人肺源性细胞和内皮细胞的直接细胞毒性。
DOI：
10.1164/ajrccm/141.1.179
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Ganz,T
中科院分区：
文献类型：
--
作者：
Okrent,DG;Lichtenstein,AK;Ganz,T
中性粒细胞在保护宿主免受微生物入侵的过程中，释放出一种强大的蛋白质库，可以潜在地损害宿主组织。防御蛋白是人多形核白细胞（PMN）颗粒的主要肽，对多种肿瘤细胞系具有广泛的杀微生物和细胞毒性。为了确定这些肽是否在中性粒细胞介导的肺损伤中发挥作用，我们用人肺源性细胞系MRC-5（肺胎儿成纤维细胞）、A549（肺泡上皮特征的肺腺癌）和人脐静脉内皮细胞（HUVEC）的原代培养物进行了铬释放试验，检测了防御蛋白和其他PMN颗粒蛋白的细胞毒性。人pmn颗粒的酸萃取物粗分馏得到四组分AD。只有部分D（主要含有防御蛋白）对所有三个靶细胞都有显著的细胞毒性。相比之下，部分A（含髓过氧化物酶和乳铁蛋白）和部分C（含溶菌酶）几乎没有影响，部分B（主要含组织蛋白酶G和弹性酶）仅对内皮细胞有害。全颗粒提取物对肺上皮细胞和成纤维细胞的细胞毒性可完全由其防御素含量来解释。部分d和防御蛋白介导的细胞毒性是浓度依赖性的，至少需要10至12小时才能显现，并被血清抑制。这些肽的作用
Neutrophlls, In the course of defending the host against microbial Invasion, release a potent arsenal of proteins that can potentially damage host tissues. Defenslns are major peptldes of human polymorphonuclear leukocyte (PMN) granules and are both broadly microbicidal and cytotoxic to several tumor cell lines. Todetermine whether these peptldes could play a role In neutrophllmediated lung Injury, we examined the cytotoxicity of defenslns and other PMN granule proteins in a chromium release assay with human lung-derlved cell lines MRC-5 (lung fetal fibroblast), A549 (lung adenocarcinoma with features of alveolar epithelium), and primary cultures of human umblll· cal vein endothelial cells (HUVEC). Crude fractionation of an acid extract of human PMNgranules yielded four fractions AD. Only fraction D (containing mostly defenslns) was significantly cytotOXic to all three target cells. In contrast, fraction A (containing myeloperoxldase and lactoferrln) and fraction C (containing lysozyme) had little effect, and fraction B (containing chiefly cathepsin G and elastase) was only injurious to endothelial cells. The cytotoxicity of whole PMNgranule extracts on pulmonary epithelial and fibroblast targeta could be completely accounted for by their defensin content. Fraction D-and defensln-medlated cytotoxicity was concentration dependent, required at least 10 to 12 h to become manifest, and was Inhibited by serum. The role of these peptldes