Prostaglandin E2 from macrophages of murine splenocyte cultures inhibits the generation of lymphokine-activated killer cell activity.

Prostaglandin E2 from macrophages of murine splenocyte cultures inhibits the generation of lymphokine-activated killer cell activity.
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来自小鼠脾细胞培养物巨噬细胞的前列腺素 E2 抑制淋巴因子激活的杀伤细胞活性的产生。

DOI:
10.1159/000217694
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发表时间:
1991
期刊:
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine
影响因子:
--
通讯作者:
Chu,TM
Chu,TM
中科院分区:
--
文献类型:
--
作者:
Ohnishi,H;Lin,TH;Nakajima,I;Chu,TM

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目前的工作研究了巨噬细胞中的前列腺素 E2 (PGE2) 与其对小鼠淋巴因子激活杀伤 (LAK) 细胞生成的抑制之间的关系。吲哚美辛与白细胞介素2(IL-2)共培养以吲哚美辛剂量反应方式增强LAK细胞活性,并以相反剂量反应方式降低相应培养上清液中的PGE2含量。 LAK细胞活性的增加与PGE2含量的减少之间具有高度显着的相关性。使用双氯芬酸获得了相同的结果。检测到外源性 PGE2 以剂量反应方式对 LAK 细胞活性产生显着抑制。多克隆抗 PGE2 抗血清通过中和培养基中的 PGE2,以剂量依赖性方式增强 LAK 细胞活性。当培养巨噬细胞亚群时,还检测到培养物上清液中 PGE2 含量的减少,并且呈吲哚美辛剂量依赖性。与正常小鼠脾细胞相比,荷瘤小鼠的整个脾细胞含有更多的巨噬细胞亚群(24% vs. 12%),培养后产生更高的 PGE2 含量和相应降低的 LAK 细胞活性。此外,PGE2 降低了蛋白激酶 C (PKC) 活性以及巨噬细胞耗尽的 T 细胞和自然杀伤样细胞产生的 LAK 细胞活性。这些结果总体表明,来自小鼠脾细胞培养物中巨噬细胞的PGE2抑制LAK细胞的生成,并且PKC可能参与了抑制机制。
The present work investigated the association between prostaglandin E2(PGE2) from macrophages and its inhibition of murine lymphokine-activated killer (LAK) cell generation. The coculture of indomethacin with interleukin-2 (IL-2) augmented LAK cell activity in an indomethacin dose-response manner, and diminished PGE2content in the corresponding culture supernatant in a reverse dose-response manner. The correlation between the increase in LAK cell activity and the decrease in PGE2content was highly significant. Identical results were obtained with diclofenac. A profound inhibition of LAK cell activity by exogenous PGE2in a dose-response manner was detected. Polyclonal anti-PGE2antiserum augmented in a dose-dependent manner the LAK cell activity, by neutralizing PGE2in the medium. A reduction of PGE2content in the culture supernatant was also detected when the macrophage subpopulations were cultured and was indomethacin dose-dependent. In comparison with that of normal mouse splenocytes, the incubation of whole splenocytes of tumor-bearing mice, which contained a greater subpopulation of macrophages (24% vs. 12 %), produced a greater PGE2content and a correspondingly depressed LAK cell activity. Additionally, PGE2reduced protein kinase C (PKC) activity along with LAK cell activity generated from macrophage-depleted T cells and natural-killer-like cells. These results overall indicate that PGE2from macrophages in murine splenocyte cultures inhibits the LAK cell generation, and PKC may be involved in the inhibition mechanism.