Enhancement of neutrophil superoxide production by preincubation with recombinant human tumor necrosis factor.
Enhancement of neutrophil superoxide production by preincubation with recombinant human tumor necrosis factor.
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DOI：
10.4049/jimmunol.139.11.3783
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发表时间：
1987-12
影响因子：
4.4
通讯作者：
R. Berkow;D. Wang;J. Larrick;R. Dodson;T. Howard
中科院分区：
文献类型：
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作者：
R. Berkow;D. Wang;J. Larrick;R. Dodson;T. Howard
肿瘤坏死因子 (TNF) 是一种 17,000 Da 的蛋白质，由暴露于内毒素的单核细胞产生。人中性粒细胞与 TNF 长时间孵育后，粘附、吞噬作用、过氧化氢释放和溶菌酶分泌均有所增加。在本研究中，评估了高度纯化的重组人 TNF 调节中性粒细胞对可溶性刺激的反应的能力。当在 37°C 下孵育长达 25 分钟时，单独的肿瘤坏死因子（0.1 至 10,000 单位/ml）无法诱导中性粒细胞超氧阴离子 (O2-) 产生、颗粒释放或聚集。然而，TNF 确实会刺激中性粒细胞 F-肌动蛋白含量出现显着的时间、剂量和温度依赖性增加。虽然中性粒细胞单独暴露于 TNF 不会导致超氧阴离子产生，但它使趋化肽、f-甲硫氨酰-亮氨酰-苯丙氨酸 (FMLP) 或肿瘤促进剂、肉豆蔻酸佛波醇乙酸酯反应的 O2- 产生增强了 278%。这种增强是时间、剂量和温度依赖性的，并且是由于更快的初始氧气产生速率。当预孵育期间存在抗TNF单克隆抗体241-1H11时，FMLP诱导的O2产生的TNF增强被阻断。 TNF 预孵育还增强 FMLP 诱导的溶菌酶释放，但对 FMLP 的聚集和肌动蛋白聚合没有影响。花生四烯酸激活 NADPH 氧化酶的动力学不受 TNF 的影响。这些结果表明，短暂暴露于重组人 TNF 能够增强或引发中性粒细胞响应第二次刺激的氧化爆发。
Tumor necrosis factor (TNF) is a 17,000-Da protein which is produced by mononuclear cells upon exposure to endotoxin. Increases in adherence, phagocytosis, hydrogen peroxide release, and lysozyme secretion have been demonstrated after prolonged incubation of human neutrophils with TNF. In this study, the ability of highly purified recombinant human TNF to modulate neutrophil responses to soluble stimuli was evaluated. Tumor necrosis factor alone (0.1 to 10,000 units/ml) failed to induce neutrophil superoxide anion (O2-) production, granule release, or aggregation when incubated for up to 25 min at 37 degrees C. TNF did, however, stimulate a significant time-, dose-, and temperature-dependent increase in neutrophil F-actin content. Although exposure of neutrophils to TNF alone caused no superoxide anion production, it enhanced the O2- production in response to the chemotactic peptide, f-methionyl-leucyl-phenylalanine (FMLP) or the tumor promotor, phorbol myristate acetate, by as much as 278%. The enhancement was time-, dose-, and temperature-dependent and was due to a more rapid initial rate of O2- production. The TNF enhancement of FMLP-induced O2- production was blocked when an anti-TNF monoclonal antibody 241-1H11, is present during the preincubation period. TNF preincubation also enhanced FMLP-induced lysozyme release, but had no effect on aggregation and actin polymerization by FMLP. The kinetics of NADPH oxidase activation by arachidonic acid was unaltered by TNF. These results indicate that brief exposures to recombinant human TNF are able to enhance or prime the neutrophil oxidative burst in response to a second stimulus.