Ohnishi H, Lin T H, Nakajima I, Chu T M
Department of Diagnostic Immunology Research and Biochemistry, Roswell Park Memorial Institute, Buffalo, N.Y.
Tumour Biol. 1991;12(2):99-110. doi: 10.1159/000217694.
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 PGE2 content in the corresponding culture supernatant in a reverse dose-response manner. The correlation between the increase in LAK cell activity and the decrease in PGE2 content was highly significant. Identical results were obtained with diclofenac. A profound inhibition of LAK cell activity by exogenous PGE2 in a dose-response manner was detected. Polyclonal anti-PGE2 antiserum augmented in a dose-dependent manner the LAK cell activity, by neutralizing PGE2 in the medium. A reduction of PGE2 content 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 PGE2 content and a correspondingly depressed LAK cell activity. Additionally, PGE2 reduced 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 PGE2 from macrophages in murine splenocyte cultures inhibits the LAK cell generation, and PKC may be involved in the inhibition mechanism.
本研究探讨了巨噬细胞产生的前列腺素E2（PGE2）与其对小鼠淋巴因子激活的杀伤（LAK）细胞生成的抑制作用之间的关联。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了LAK细胞活性，并以相反的剂量反应方式降低了相应培养上清液中的PGE2含量。LAK细胞活性增加与PGE2含量降低之间的相关性非常显著。双氯芬酸也得到了相同的结果。检测到外源性PGE2以剂量反应方式对LAK细胞活性有显著抑制作用。多克隆抗PGE2抗血清通过中和培养基中的PGE2以剂量依赖方式增强了LAK细胞活性。当培养巨噬细胞亚群时，也检测到培养上清液中PGE2含量降低，且呈吲哚美辛剂量依赖性。与正常小鼠脾细胞相比，荷瘤小鼠全脾细胞（其中巨噬细胞亚群比例更高，分别为24%和12%）孵育产生的PGE2含量更高，相应地LAK细胞活性降低。此外，PGE2降低了蛋白激酶C（PKC）活性以及从去除巨噬细胞的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，小鼠脾细胞培养物中巨噬细胞产生的PGE2抑制LAK细胞生成，PKC可能参与了抑制机制。
