Alveolar macrophage apoptosis and TNF-α, but not p53, expression correlate with murine response to bleomycin.
Alveolar macrophage apoptosis and TNF-α, but not p53, expression correlate with murine response to bleomycin.
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肺泡巨噬细胞凋亡和 TNF-α（而非 p53）表达与小鼠对博来霉素的反应相关。
DOI：
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
M. Friedman
中科院分区：
文献类型：
--
作者：
L. Ortiz;Kryztof Moroz;Jing‐Yao Liu;G. Hoyle;T. Hammond;R. Hamilton;A. Holian;W. Banks;A. Brody;M. Friedman
细胞凋亡被认为是一种限制肺损伤的保护机制。然而，细胞凋亡可能导致损伤肺的炎症负担。博来霉素暴露小鼠（BLM）是研究肺损伤的一种成熟模型。BLM暴露诱导DNA损伤，增强肺组织中肿瘤坏死因子(TNF)-α的表达。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）中，研究了细胞凋亡的诱导[通过光镜变化（2、8、12、24、48和72 h）和流式细胞术（24 h）的膜联蛋白V摄取]，TNF-α的分泌（通过ELISA测定）和p53的表达（通过免疫印迹法）。BLM诱导两种小鼠AM细胞凋亡，而非载药。膜联蛋白V摄取显示，C57BL/6小鼠（52.9%）的AM凋亡数量明显高于BALB/c小鼠（40.8%）（P < 0.001）。BLM诱导AM细胞凋亡之前，C57BL/6小鼠的TNF-α分泌增加，而BALB/c小鼠则没有。此外，与C57BL/6和BALB/c小鼠相比，C57BL/6背景下的双TNF-α受体缺陷小鼠的凋亡AM数量显著减少（P < 0.001）。BLM还增强了两种小鼠AM中p53的表达。然而，p53缺陷小鼠发生blm诱导的肺损伤，表现出类似的肺细胞增殖（通过增殖细胞核抗原免疫染色测量），并且与C57BL/6小鼠（62±6.5 μg/肺）积累相似的肺羟脯氨酸量（65±6.9 μg/肺）。因此，AM凋亡在BLM诱导的肺损伤中发生，其方式与小鼠对BLM的应变敏感性相关。此外，TNF-α的分泌而不是p53的表达导致了小鼠品系对BLM的反应差异。肿瘤坏死因子；应变敏感性。
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)-α 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-α (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-α in C57BL/6 but not in BALB/c mice. Furthermore, double TNF-α 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 μg/lung) as did C57BL/6 (62 ± 6.5 μg/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-α secretion rather than p53 expression contributes to the difference in murine strain response to BLM. tumor necrosis factor; strain susceptibility.
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[3H]博来霉素 A2 在小鼠体内的肺部命运。
DOI：
--
发表时间：
1984
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Lazo,JS;Pham,ET
通讯作者：
Pham,ET
博来霉素的急性肺毒性：博莱霉素敏感和耐药品系小鼠的 DNA 断裂和基质蛋白 mRNA 水平。
影响因子：
3.6
作者：
HarrisonJr,JH;Hoyt,DG;Lazo,JS
通讯作者：
Lazo,JS
影响因子：
15.9
作者：
POLUNOVSKY, VA;CHEN, B;BITTERMAN, PB
通讯作者：
BITTERMAN, PB
影响因子：
1.7
作者：
PHAN, SH;KUNKEL, SL
通讯作者：
KUNKEL, SL
影响因子：
56.9
作者：
SMITH, ML;CHEN, IT;FORNACE, AJ
通讯作者：
FORNACE, AJ