Dushkin M, Schwartz Y, Volsky N, Musatov M, Vereschagin E, Ragino J, Perminova O, Kozlov V
Laboratory of Atherogenesis, Russian Academy of Medical Science, Novosibirsk, Russia.
Prostaglandins Other Lipid Mediat. 1998 Mar;55(4):219-36. doi: 10.1016/s0090-6980(98)00024-0.
Oxygenated derivatives of cholesterol (oxysterols), found in high concentrations in atherosclerotic lesions, are potent immunosuppressive agents inhibiting T-cell responses to different stimuli. The action of oxysterols on macrophage functions and macrophage-lymphocyte interaction has been poorly investigated. In this work, the effects of 25-hydroxycholesterol (25-OHCh) and 7-ketocholesterol (7-KCh) upon some functions of murine peritoneal macrophage (PM), such as generation of reactive oxygen intermediates (ROI), secretion of neopterin and interleukin-1 (IL-1)-like activity, Fc-receptor (FcR) activity, and murine and human lymphocyte functions, participating in lymphocyte-macrophage interactions, such as macrophage-activating factor (MAF) and Ia-inducing factor (IaIF) secretion, were studied in vitro. 7-KCh in concentration of 5 micrograms/mL culture medium only, but not 25-OHCh, significantly inhibited ROI generation by zymosan-stimulated PM. Pretreatment of PM for 22 h with 25-OHCh and 7-KCh led to the decrease of IL-1-like activity secretion. 25-OHCh and 7-KCh inhibited both FcR-dependent binding and phagocytosis of sheep red blood cells (SRBC). Oxysterols did not change both spontaneous and lipopolysaccharide-stimulated secretion of neopterin by PM. 25-OHCh dose-dependently and more efficiently than 7-KCh inhibited murine splenocyte secretion of MAF, which activity was determined by the ability of splenocyte-conditioned medium to stimulate ROI generation in PM. Both 25-OHCh and 7-KCh inhibited significantly proliferative activity of human mixed lymphocyte culture (MLC), as well as lymphocyte secretion of IaIF, which stimulates the expression of HLA antigens in cultured human monocytes. Purified Ch did not alter these parameters. These data showed, that some inflammatory functions of macrophages and lymphocytes may be modified by such environmental conditions as the presence of oxysterols.
胆固醇的氧化衍生物（氧化甾醇）在动脉粥样硬化病变中含量很高，是抑制T细胞对不同刺激反应的强效免疫抑制剂。氧化甾醇对巨噬细胞功能和巨噬细胞-淋巴细胞相互作用的影响研究较少。在本研究中，体外研究了25-羟基胆固醇（25-OHCh）和7-酮胆固醇（7-KCh）对小鼠腹腔巨噬细胞（PM）某些功能的影响，如活性氧中间体（ROI）的产生、新蝶呤的分泌和白细胞介素-1（IL-1）样活性、Fc受体（FcR）活性，以及参与淋巴细胞-巨噬细胞相互作用的小鼠和人类淋巴细胞功能，如巨噬细胞激活因子（MAF）和Ia诱导因子（IaIF）的分泌。仅在培养基浓度为5微克/毫升时，7-KCh而非25-OHCh能显著抑制酵母聚糖刺激的PM产生ROI。用25-OHCh和7-KCh预处理PM 22小时导致IL-1样活性分泌减少。25-OHCh和7-KCh均抑制FcR依赖的绵羊红细胞（SRBC）结合和吞噬。氧化甾醇不改变PM自发和脂多糖刺激的新蝶呤分泌。25-OHCh剂量依赖性地且比7-KCh更有效地抑制小鼠脾细胞分泌MAF，MAF的活性由脾细胞条件培养基刺激PM产生ROI的能力决定。25-OHCh和7-KCh均显著抑制人混合淋巴细胞培养（MLC）的增殖活性以及淋巴细胞分泌IaIF，IaIF刺激培养的人单核细胞中HLA抗原的表达。纯化的胆固醇不改变这些参数。这些数据表明，巨噬细胞和淋巴细胞的一些炎症功能可能会受到氧化甾醇存在等环境条件的影响。
