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首页> 外文期刊>American Journal of Physiology >Alveolar macrophage apoptosis and TNF-alpha, but not p53, expression correlate with murine response to bleomycin.
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Alveolar macrophage apoptosis and TNF-alpha, but not p53, expression correlate with murine response to bleomycin.

机译：肺泡巨噬细胞凋亡和TNF-α（而非p53）表达与鼠对博来霉素的反应有关。

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Apoptosis is considered to be a protective mechanism that limits lung injury. However, apoptosis might contribute to the inflammatory burden present in the injured lung. The exposure of mice to bleomycin (BLM) is a well-established model for the study of lung injury. BLM exposure induces DNA damage and enhances tumor necrosis factor (TNF)-alpha expression in the lung. To evaluate the importance of alveolar macrophage (AM) apoptosis in the pathogenesis of lung injury, we exposed BLM-sensitive (C57BL/6) and BLM-resistant (BALB/c) mice to BLM (120 mg/kg) and studied the induction of apoptosis [by light-microscopy changes (2, 8, 12, 24, 48, and 72 h) and annexin V uptake by flow cytometry (24 h)], the secretion of TNF-alpha (measured by ELISA), and the expression of p53 (by immunoblotting) in AM retrieved from these mice. BLM, but not vehicle, induced apoptosis in AM from both murine strains. The numbers of apoptotic AM were significantly greater (P < 0.001) in C57BL/6 mice (52.9%) compared with BALB/c mice (40.8%) as demonstrated by annexin V uptake. BLM induction of apoptosis in AM was preceded by an increased secretion of TNF-alpha in C57BL/6 but not in BALB/c mice. Furthermore, double TNF-alpha receptor-deficient mice, developed on a C57BL/6 background, demonstrated significantly (P < 0.001) lower numbers of apoptotic AM compared with C57BL/6 and BALB/c mice. BLM also enhanced p53 expression in AM from both murine strains. However, p53-deficient mice developed BLM-induced lung injury, exhibited similar lung cell proliferation (measured as proliferating cell nuclear antigen immunostaining), and accumulated similar amounts of lung hydroxyproline (65 +/- 6.9 microgram/lung) as did C57BL/6 (62 +/- 6.5 microgram/lung) mice. Therefore, AM apoptosis is occurring during BLM-induced lung injury in a manner that correlates with murine strain sensitivity to BLM. Furthermore, TNF-alpha secretion rather than p53 expression contributes to the difference in murine strain response to BLM.tumor necrosis factor; strain susceptibility
机译：细胞凋亡被认为是限制肺损伤的保护机制。但是，细胞凋亡可能会导致受伤肺部的炎症负担。小鼠暴露于博来霉素（BLM）是研究肺损伤的公认模型。 BLM暴露会诱导DNA损伤并增强肺中的肿瘤坏死因子（TNF）-α表达。为了评估肺泡巨噬细胞（AM）凋亡在肺损伤发病机制中的重要性，我们将BLM敏感（C57BL / 6）和BLM耐药（BALB / c）小鼠暴露于BLM（120 mg / kg），并研究了诱导方法细胞凋亡[通过光学显微镜变化（2、8、12、24、48和72小时）和流式细胞仪（24小时）摄取膜联蛋白V的摄取]，TNF-α的分泌（通过ELISA测定）和从这些小鼠中回收的AM中p53的表达（通过免疫印迹）。 BLM，而不是媒介物，都诱导了两种鼠类菌株的AM凋亡。如通过膜联蛋白V摄取所证实，与BALB / c小鼠（40.8％）相比，C57BL / 6小鼠（52.9％）中的凋亡AM数目显着更大（P <0.001）。 BLM诱导AM凋亡的过程是在C57BL / 6中增加了TNF-α的分泌，但在BALB / c小鼠中却没有。此外，与C57BL / 6和BALB / c小鼠相比，在C57BL / 6背景上发育的双TNF-α受体缺陷型小鼠表现出凋亡AM的数量显着降低（P <0.001）。 BLM还增强了两种鼠类菌株在AM中的p53表达。但是，p53缺陷小鼠发生了BLM诱导的肺损伤，表现出与C57BL / 6相似的肺细胞增殖（以增殖细胞核抗原免疫染色测量），并且积累了类似量的肺羟脯氨酸（65 +/- 6.9微克/肺）。 （62 +/- 6.5微克/肺）小鼠。因此，在BLM诱导的肺损伤期间，AM凋亡以与鼠类菌株对BLM的敏感性相关的方式发生。此外，TNF-α的分泌而不是p53的表达导致鼠株对BLM的反应有所不同。应变敏感性

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