Tsai C Y, Yu C L, Hsieh S C, Liao T S, Lin W M
Department of Medicine, Veterans General Hospital-Taipei, Taiwan, R.O.C.
Zhonghua Yi Xue Za Zhi (Taipei). 1995 Sep;56(3):143-51.
Prostaglandin E2 (PGE2) is a feedback suppressor of immune response. Beta 2-Microglobulin (beta 2M) is part of HLA class I molecule that mediates viral antigen presentation to cytotoxic T lymphocytes as well as graft rejection. It has been known that beta 2M can be synthesized by both stimulated and unstimulated lymphocytes, but it is unknown whether beta 2M can be modulated by PGE2. This investigation aimed to clarify this point.
Normal human mononuclear cells (MNC) were isolated, stimulated by phytohemagglutinin (PHA), and cultured for 3 days in the presence or absence of PGE2. The culture supernatants were collected and detected for beta 2M concentration by enzyme linked immunosorbent assays (ELISA). The cell pellets were stained indirectly with immunofluorescence for HLA-class I antigen and beta 2M expression on the surface membranes. In addition, the membrane potential of stimulated or unstimulated cells was measured by flow cytometry to evaluate the effect exerted by PGE2.
PGE2 at a concentration of more than 1 x 10(-8)M markedly suppressed the expression and release of beta 2M from PHA-stimulated MNC in a dose-dependent manner. Expression of HLA-class I molecule on PHA-stimulated MNC was also suppressed by PGE2. Kinetic study demonstrated that PGE2 began to suppress beta 2M synthesis of PHA-stimulated MNC from the 3rd day of culture. It also inhibited beta 2M release from lymphocytes in mixed lymphocyte reaction. This inhibitory effect was not due to cell death as confirmed by trypan blue exclusion. PGE2 per se exerts negligible effect on membrane potential of MNC but can normalize the depolarized state of the membrane induced by PHA as demonstrated by 3,3'-dihexyloxacarbocyanine iodide stain.
PGE2 down-regulates the production of HLA-class I antigens and beta 2M molecules. This effect is associated with the suppression of cytotoxic T cell function by PGE2 and may be relevant to the underlying mechanism of PGE2 on this population of cells.
前列腺素E2（PGE2）是免疫反应的反馈抑制因子。β2-微球蛋白（β2M）是HLA I类分子的一部分，介导病毒抗原呈递给细胞毒性T淋巴细胞以及移植排斥反应。已知β2M可由受刺激和未受刺激的淋巴细胞合成，但β2M是否可被PGE2调节尚不清楚。本研究旨在阐明这一点。
分离正常人单核细胞（MNC），用植物血凝素（PHA）刺激，并在有或无PGE2的情况下培养3天。收集培养上清液，通过酶联免疫吸附测定（ELISA）检测β2M浓度。细胞沉淀用免疫荧光间接染色，以检测表面膜上的HLA I类抗原和β2M表达。此外，通过流式细胞术测量受刺激或未受刺激细胞的膜电位，以评估PGE2的作用。
浓度超过1×10^(-8)M的PGE2以剂量依赖方式显著抑制PHA刺激的MNC中β2M的表达和释放。PGE2也抑制PHA刺激的MNC上HLA I类分子的表达。动力学研究表明，PGE2从培养第3天开始抑制PHA刺激的MNC中β2M的合成。它还抑制混合淋巴细胞反应中淋巴细胞释放β2M。台盼蓝排斥试验证实这种抑制作用不是由于细胞死亡。PGE2本身对MNC的膜电位影响可忽略不计，但如用3,3'-二己基氧杂羰花青碘化物染色所示，它可使PHA诱导的膜去极化状态恢复正常。
PGE2下调HLA I类抗原和β2M分子的产生。这种作用与PGE2对细胞毒性T细胞功能的抑制有关，可能与PGE2对这群细胞的潜在作用机制有关。
