Salageanu A, Ceacareanu B, Istrate N, Szegli G
Immunology Department, Cantacuzino Institute, Bucharest, Romania.
Roum Arch Microbiol Immunol. 1997 Jan-Jun;56(1-2):27-35.
We previously reported that the bacterial immunomodulator CANTASTIM inhibited the LPS-induced TNF-alpha production in murine macrophages both in vivo and in vitro. In this report, we compared the activity of CANTASTIM with that of two phospholipids (cardiolipin and phosphatidylethanolamine) which are among the components of its lipid fraction. We noticed a significant reduction in the production of TNF-alpha upon stimulation with LPS in murine peritoneal macrophages pretreated for at least 3 h with CANTASTIM or cardiolipin. CANTASTIM was active at much lower concentrations than cardiolipin. Preliminary experiments with partially deacylated CANTASTIM indicated some decrease of TNF-alpha secretion. However, further studies are necessary to clarify this matter. Also, while CANTASTIM and its partially deacylated derivative could trigger the TNF-alpha secretion in murine macrophages, individual phospholipids did not. Based on these results, we concluded that CANTASTIM could induce the TNF-alpha suppression by multiple mechanisms, including the induction of regulatory cytokines such as IL-10 and CD14 receptor blockade/downregulation.
我们之前报道过，细菌免疫调节剂CANTASTIM在体内和体外均能抑制小鼠巨噬细胞中脂多糖（LPS）诱导的肿瘤坏死因子-α（TNF-α）产生。在本报告中，我们将CANTASTIM的活性与两种磷脂（心磷脂和磷脂酰乙醇胺）进行了比较，这两种磷脂是其脂质部分的成分。我们注意到，用CANTASTIM或心磷脂预处理至少3小时的小鼠腹腔巨噬细胞在用LPS刺激后，TNF-α的产生显著减少。CANTASTIM在比心磷脂低得多的浓度下就具有活性。对部分脱酰基的CANTASTIM进行的初步实验表明TNF-α分泌有所减少。然而，需要进一步研究来阐明此事。此外，虽然CANTASTIM及其部分脱酰基衍生物可触发小鼠巨噬细胞中的TNF-α分泌，但单个磷脂则不能。基于这些结果，我们得出结论，CANTASTIM可通过多种机制诱导TNF-α抑制，包括诱导调节性细胞因子如白细胞介素-10以及CD14受体阻断/下调。
