Ophir R, Ben-Efraim S, Bonta I L
Int J Tissue React. 1987;9(3):189-94.
Leukotriene C4, the precursor of leukotriene D4 (LTD4), was earlier shown to activate macrophages, as indicated by lysosomal enzyme discharge. This event is limited by LT-induced secretion of PGE2, which inhibits the functions of these cells. The circumstance that activated macrophages may exert cytostatic activity towards tumour cells prompted us to study the effect of LTD4 and indomethacin on the cytostatic activity of macrophages as expressed by inhibition of [3H]thymidine incorporation in MOPC-315 plasmacytoma tumour cells. Decrease in incorporation, caused by separate administration of the two substances, was additively enhanced upon exposure of the co-culture of macrophages and tumour cells to the two substances simultaneously. Tumour cells alone are not affected by the substances, but the low rate of thymidine incorporation by macrophages alone was increased by LTD4 in the presence of indomethacin. Decrease of thymidine incorporation into tumour cells co-cultured with macrophages is attributed to a macrophage-mediated, rather than to a direct, influence of LTD4 and indomethacin on tumour cells. An increase in macrophage-mediated cytostasis by LTD4 requires the inhibition of endogenous PGE2 production in macrophages.
白三烯C4是白三烯D4（LTD4）的前体，先前的研究表明，它可激活巨噬细胞，表现为溶酶体酶释放。这一过程受LT诱导的PGE2分泌的限制，PGE2可抑制这些细胞的功能。鉴于活化的巨噬细胞可能对肿瘤细胞发挥细胞抑制活性，我们开展了本研究，以探究LTD4和吲哚美辛对巨噬细胞细胞抑制活性的影响，该活性通过抑制MOPC - 315浆细胞瘤肿瘤细胞中[3H]胸腺嘧啶核苷掺入来体现。单独给予这两种物质均可导致掺入减少，当巨噬细胞与肿瘤细胞的共培养物同时暴露于这两种物质时，掺入减少的程度呈相加性增强。单独的肿瘤细胞不受这些物质影响，但在吲哚美辛存在的情况下，LTD4可使单独培养的巨噬细胞的低胸腺嘧啶核苷掺入率升高。与巨噬细胞共培养的肿瘤细胞中胸腺嘧啶核苷掺入减少，归因于巨噬细胞介导的作用，而非LTD4和吲哚美辛对肿瘤细胞的直接影响。LTD4增强巨噬细胞介导的细胞抑制作用需要抑制巨噬细胞内源性PGE2的产生。
