Cell surface regulation of silica-induced apoptosis by the SR-A scavenger receptor in a murine lung macrophage cell line (MH-S)
Cell surface regulation of silica-induced apoptosis by the SR-A scavenger receptor in a murine lung macrophage cell line (MH-S)
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DOI：
10.1006/taap.2001.9190
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发表时间：
2001-07-01
影响因子：
3.8
通讯作者：
Holian, A
中科院分区：
文献类型：
--
作者：
Chao, SL;Hamilton, RF;Holian, A
清道夫受体 (SR) 负责识别从氧化 LDL（内源性）到可吸入颗粒物（外源性）等多种配体。最近的许多研究表明这些 SR 配体诱导巨噬细胞凋亡。然而，SR 触发细胞凋亡的机制尚不清楚。本研究使用小鼠肺泡巨噬细胞系 (MH-S) 来研究 SR 在 caspase 激活中的作用。通过 FACS 分析证实了 MH-S 细胞上 SR 的存在，并且与小鼠肺泡巨噬细胞上发现的分布相似。在使用或不使用 SR 阻断剂的情况下，将半胱天冬酶 1、3 和 6 的活性暴露于结晶二氧化硅 6 小时后进行测量。 Caspase 活性通过特定显色底物的水解和活性酶形式的形成（Western 为活性 caspase 3）来测定。二氧化硅刺激 MH-S 细胞显着的 caspase 活性、细胞凋亡和坏死，2F8（一种阻断抗体）和聚肌苷酸（一种非特异性 SR 拮抗剂）可减弱这种活性。结果表明，SR 对于巨噬细胞中由二氧化硅引起的 caspase 激活和随后的细胞凋亡（以及坏死）是必需的。 (C) 2001 年学术出版社。
Scavenger receptors (SR) are responsible for recognition of ligands as diverse as oxidized LDL (endogenous) to respirable particulates (exogenous). A number of recent studies have suggested that these SR ligands induce apoptosis of macrophages. However, the mechanism by which SR triggers apoptosis is not understood. This study used a murine alveolar macrophage cell line (MH-S) to investigate the role of the SR in caspase activation. The presence of SR on MH-S cells was confirmed by FACS analysis and was similar to the distribution found on murine alveolar macrophages. The activity of caspases 1, 3, and 6 was measured following a 6-h exposure to crystalline silica with and without blockers of the SR. Caspase activities were determined by hydrolysis of specific chromogenic substrates and formation of an active enzymatic form (Western for active caspase 3). Silica stimulated significant caspase activity, apoptosis, and necrosis of MH-S cells, which was attenuated by 2F8 (a blocking antibody) and polyinosinic acid (a nonspecific SR antagonist). The results indicate that the SR are necessary for caspase activation and subsequent apoptosis (as well as necrosis) caused by silica in macrophage cells. (C) 2001 Academic Press.