A tumor necrosis factor mimetic peptide activates a murine macrophage cell line to inhibit mycobacterial growth in a nitric oxide-dependent fashion
A tumor necrosis factor mimetic peptide activates a murine macrophage cell line to inhibit mycobacterial growth in a nitric oxide-dependent fashion
复制标题
DOI：
10.1128/iai.66.5.2122-2127.1998
复制
发表时间：
1998-05-01
影响因子：
3.1
通讯作者：
Briscoe, H
中科院分区：
文献类型：
--
作者：
Britton, WJ;Meadows, N;Briscoe, H
分枝杆菌感染的控制依赖于细胞因子介导的单核巨噬细胞的激活来抑制细胞内分枝杆菌的生长。最佳的激活需要T细胞衍生的干扰素和其他信号的存在，包括肿瘤坏死因子。最近，一种基于人肿瘤坏死因子序列70-80位氨基酸的11肽被发现具有类似肿瘤坏死因子的特性，包括激活人和小鼠中性粒细胞杀死疟原虫。因此，我们研究了人肿瘤坏死因子(70-80)对感染卡介苗的小鼠巨噬细胞株RAW264.7的激活能力，当人肿瘤坏死因子或肿瘤坏死因子(70-80)在干扰素-γ存在下预处理RAW264.7细胞时，通过摄取H-3标记的尿嘧啶和通过培养上清液中的亚硝酸盐测定伴随的一氧化氮的释放，卡介苗的复制呈剂量依赖性的减少。肿瘤坏死因子或肿瘤坏死因子(70-80)诱导的巨噬细胞活化依赖于干扰素-γ，可被人肿瘤坏死因子中和抗体和抗肿瘤坏死因子-γ抗血清抑制，亚硝酸盐释放和卡介苗生长抑制均被L精氨酸竞争性抑制剂阻断诱导型一氧化氮合酶的激活。一种可溶性的1型肿瘤坏死因子受体阻断了人肿瘤坏死因子和肿瘤坏死因子(70-80)对卡介苗感染的巨噬细胞的激活，表明肿瘤坏死因子(70-80)的作用依赖于通过肿瘤坏死因子受体I的信号转导。体外模拟巨噬细胞激活的效应提示，肿瘤坏死因子(70-80)治疗可能调节体内分枝杆菌感染。
The control of mycobacterial infections depends on the cytokine-mediated activation of mononuclear phagocytes to inhibit the growth of intracellular mycobacteria. Optimal activation requires the presence of T-cell-derived gamma interferon (IFN-gamma) and other signals, including tumor necrosis factor (TNF). Recently, an 11-mer peptide based on amino acids 70 to 80 of the human TNF sequence, TNF(70-80), was found to have TNF mimetic properties, which include the activation of human and mouse neutrophils to kill Plasmodia spp, Therefore, we investigated the capacity of TNF(70-80) to activate the murine macrophage cell line RAW264.7 infected with the vaccine strain Mycobacterium bovis bacillus Calmette-Guerin (BCG), When RAW264.7 cells were pretreated with human TNF or TNF(70-80) in the presence of IFN-gamma, there was a dose-dependent reduction in the replication of BCG as measured by the uptake of H-3-labeled uracil and a concomitant release of nitric oxide as measured by the nitrite in the culture supernatants. TNF- or TNF(70-80)-induced macrophage activation was dependent on IFN-gamma and was inhibited by neutralizing monoclonal antibody to human TNF and by anti-TFN-gamma antisera, Both nitrite release and BCG growth inhibition were abrogated by competitive inhibitors of L-arginine, which blocked the activation of inducible nitric oxide synthase. A soluble form of the Type 1 TNF receptor blocked the activation of BCG-infected macrophages by human TNF and TNF(70-80), demonstrating that the effect of TNF(70-80) is dependent on signaling through TNF receptor I. The mimetic effects of TNF(70-80) on macrophage activation in vitro suggest that treatment with TNF(70-80) may modulate mycobacterial infections in vivo.