Radka S F, Nakamura S, Sakurada S, Salahuddin S Z
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, WA 98121.
J Immunol. 1993 Jun 1;150(11):5195-201.
Oncostatin M (OM), a 30-kDa glycoprotein, recently was identified as a major growth-promoting factor in the conditioned medium (CM) of the 38-0 cell line, a CD4,+ chronically human T lymphotropic virus type (HTLV)-II-infected, transformed T cell line. CM 38-0 induced the proliferation of spindle cells cultured in vitro from AIDS-associated Kaposi's sarcoma (AIDS-KS) cells. To determine how much of the AIDS-KS cell growth activity present in 38-0 CM was because of the presence of OM, we depleted OM by using specific mAb-affinity chromatography. OM purified from this CM stimulated AIDS-KS cell growth in a concentration-dependent fashion. The effluent, completely depleted of OM, failed to induce growth of AIDS-KS cells. To detect the constitutive release of OM by cells acutely or chronically infected with either HTLV-I, HTLV-II, or HIV-1, we utilized an enzyme-linked immunoassay. Whereas the chronically infected cells released significant levels of OM, the acutely infected cells released little or no OM. The presence of OM in HIV-1-infected T-cell CM correlated completely with AIDS-KS cell growth activity. Infrequently, low level AIDS-KS cell growth activity was seen in the absence of OM. This correlated with relatively high levels of IL-6 in the CM. In a CM-containing OM in the absence of detectable IL-6, a neutralizing antibody to OM completely abrogated KS cell growth activity. The presence of specific oncostatin M receptors on the KS cell lines was confirmed by cross-linking experiments. The results shown here suggest that T cells chronically infected with HIV-1 can secrete OM, which may play a role in the initiation or progression of AIDS-KS lesions, either alone, or in concert with IL-6.
抑瘤素M（OM）是一种30 kDa的糖蛋白，最近被确定为38 - 0细胞系条件培养基（CM）中的一种主要生长促进因子，38 - 0细胞系是一种被人嗜T淋巴细胞病毒II型（HTLV - II）慢性感染的CD4⁺转化T细胞系。38 - 0细胞系的条件培养基能诱导从艾滋病相关卡波西肉瘤（AIDS - KS）细胞体外培养的纺锤体细胞增殖。为了确定38 - 0细胞系条件培养基中存在的AIDS - KS细胞生长活性有多少是由于OM的存在，我们使用特异性单克隆抗体亲和层析法去除OM。从这种条件培养基中纯化的OM以浓度依赖的方式刺激AIDS - KS细胞生长。完全去除OM的流出物未能诱导AIDS - KS细胞生长。为了检测急性或慢性感染HTLV - I、HTLV - II或HIV - 1的细胞对OM的组成性释放，我们采用了酶联免疫吸附测定法。虽然慢性感染的细胞释放出大量的OM，但急性感染的细胞释放很少或不释放OM。HIV - 1感染的T细胞条件培养基中OM的存在与AIDS - KS细胞生长活性完全相关。在没有OM的情况下，偶尔会观察到低水平的AIDS - KS细胞生长活性。这与条件培养基中相对较高水平的IL - 6相关。在不含可检测到的IL - 6但含有OM的条件培养基中，针对OM的中和抗体完全消除了卡波西肉瘤细胞的生长活性。通过交联实验证实了卡波西肉瘤细胞系上存在特异性抑瘤素M受体。此处所示结果表明，慢性感染HIV - 1的T细胞可分泌OM，其可能单独或与IL - 6协同在AIDS - KS病变的起始或进展中发挥作用。
