Macrophage-mediated tumor cell killing: regulation of expression of cytolytic activity by prostaglandin E.
Macrophage-mediated tumor cell killing: regulation of expression of cytolytic activity by prostaglandin E.
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巨噬细胞介导的肿瘤细胞杀伤：前列腺素 E 调节细胞溶解活性的表达。
DOI：
10.4049/jimmunol.126.2.424
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发表时间：
1981
影响因子：
4.4
通讯作者：
S. Russell
中科院分区：
文献类型：
--
作者：
S. Taffet;S. Russell
非特异性巨噬细胞介导的体外杀瘤活性的表达是一种短暂的现象。本文报道的工作表明，小鼠巨噬细胞的杀肿瘤活性的丧失至少部分归因于前列腺素E（PGE）的作用。抑制细胞溶解活性表达所需的PGE量（2 × 10（-9）M）很容易由暴露于100 ng/ml细菌脂多糖（LPS）诱导杀死肿瘤细胞的同一群常驻腹腔巨噬细胞合成和分泌。巨噬细胞暴露于LPS后1小时内，上清液中存在抑制浓度的PGE。尽管如此，细胞溶解活性仍然发展，并且需要12至16小时的PGE具有其完全的抑制作用。因此，PGE不通过阻断细胞溶解活性的发展来起作用。用10（-6）M吲哚美辛（或其他环氧合酶抑制剂）处理LPS刺激的巨噬细胞，可阻止PGE合成和细胞溶解活性的关闭。后一种效应可以通过向培养物中加入浓度为10（-8）M的PGE 2来逆转。最后，PGE抑制吲哚美辛处理的巨噬细胞介导的细胞溶解活性，只有当激活剂存在：脉冲与PGE之前，添加LPS有一个可以忽略不计的抑制作用。这些发现可能有助于解释为什么肿瘤内巨噬细胞往往缺乏非特异性细胞溶解能力。
The expression of nonspecific macrophage-mediated tumoricidal activity in vitro is a transient phenomenon. The work reported here shows that the loss of tumoricidal activity by mouse macrophages is attributable, at least in part, to the effects of prostaglandin E (PGE). The amount of PGE needed to inhibit the expression of cytolytic activity (2 x 10(-9) M) was readily synthesized and secreted by the same population of resident peritoneal macrophages that had been induced to kill tumor cells by exposure to 100 ng/ml bacterial lipopolysaccharide (LPS). Inhibitory concentrations of PGE were present in supernatants within the 1st hr after macrophages were exposed to LPS. In spite of this fact, cytolytic activity still developed, and 12 to 16 hr were required for the PGE to have its full inhibitory effect. Thus, PGE did not act by blocking the development of cytolytic activity. Treatment of LPS-stimulated macrophages with 10(-6) M indomethacin (or other cyclooxygenase inhibitors) prevented both PGE synthesis and the shut-off of cytolytic activity. The latter effect could be reversed by adding PGE2 to the cultures at a concentration of 10(-8) M. Lastly, PGE inhibited cytolytic activity mediated by indomethacin-treated macrophages only when activator was present: pulsing with PGE before the addition of LPS had a negligible inhibitory effect. These findings may help explain why intratumoral macrophages often lack nonspecific cytolytic capabilities.