Dieter P, Ambs P, Fitzke E, Hidaka H, Hoffmann R, Schwende H
Biochemical Institute, University of Freiburg, Germany.
J Immunol. 1995 Sep 1;155(5):2595-604.
LPS and liposome-encapsulated MTP-PE induce liver macrophages cytotoxicity against tumor target cells and a release of TNF-alpha, nitric oxide, and eicosanoids but not a generation of superoxide anions. Neither agent elicits a formation of inositol phosphates, a change in intracellular free calcium, or a translation of protein kinase C-beta. Inhibition or down-regulation of protein kinase C does not inhibit the release of TNF-alpha and nitric oxide but inhibits the formation of prostanoids. In contrast to LPS, liposome -encapsulated MTP-PE induces an elevation of diacylglycerol mass and an enhanced expression of protein kinase C-delta. LPS, but not liposome-encapsulated MTP-PE, elicits an enhanced expression of cytosolic phospholipase A2 and a predominant formation of PGE2. Both agents elicit different responses when given to cells pretreated with one of the immunomodulators, with dexamethasone, or with PGE2. In contrast, to liposome-encapsulated MTP-PE, LPS induces only cytotoxicity when added to liver macrophages simultaneously or a maximum of 2 h before the addition of tumor target cells. The observed differences might reflect partly differences in the potencies of LPS and some liposome-encapsulated MTP-PE as immunomodulators.
脂多糖（LPS）和脂质体包裹的MTP - PE可诱导肝巨噬细胞对肿瘤靶细胞产生细胞毒性，并释放肿瘤坏死因子 - α（TNF - α）、一氧化氮和类花生酸，但不会产生超氧阴离子。这两种物质均不会引发肌醇磷酸的形成、细胞内游离钙的变化或蛋白激酶C - β的翻译。蛋白激酶C的抑制或下调不会抑制TNF - α和一氧化氮的释放，但会抑制前列腺素的形成。与LPS不同，脂质体包裹的MTP - PE可诱导二酰基甘油含量升高以及蛋白激酶C - δ的表达增强。LPS可引发胞质磷脂酶A2的表达增强以及PGE2的主要形成，而脂质体包裹的MTP - PE则不会。当将这两种物质给予用免疫调节剂之一、地塞米松或PGE2预处理过的细胞时，它们会引发不同的反应。相比之下，与脂质体包裹的MTP - PE不同，LPS在与肝巨噬细胞同时添加或在添加肿瘤靶细胞前最多2小时添加时，仅诱导细胞毒性。观察到的差异可能部分反映了LPS和某些脂质体包裹的MTP - PE作为免疫调节剂的效力差异。
