Gene cloning of a novel cytokine inducing ICAM-1

淋巴瘤细胞与血管内皮细胞之间的相互作用是淋巴瘤细胞迁移的第一个关键步骤。我们发现侵袭性人CCRF-CEM T淋巴瘤细胞(CEM)释放一种能上调血管内皮细胞表面黏附分子表达的因子。细胞酶联免疫吸附试验(ELISA)显示CEM上清液(CEM-SUP)以时间和剂量依赖的方式增加ICAM-1和ELAM-1的表达。而CEM-SUP对内皮细胞VCAM-1的诱导作用相对较弱。ELISA检测CEM-SUP中未检测到IL-1α、IL-1β、干扰素-γ或肿瘤坏死因子α的表达。逆转录聚合酶链式反应(RT-PCR)检测到CEM-SUP中有少量肿瘤坏死因子α的表达，但不表达IL-1β和干扰素-γ。此外，细胞因子的抗体不能抑制CEM-SUP的上调作用。该因素对热(65ﾟC，30min)稳定，对酸(PH2)不稳定。凝胶过滤和层析聚焦估计其分子量为50，等电点为ph7.2。该因子的产生可能通过上调EC上的黏附分子而促进CEM的侵袭性。

The interaction between lymphoma cells and vascular endothelial cells (EC) is the first critical step in the ivasion of lymphoma cells. We found that invasive human CCRF-CEM T lymphoma cells (CEM) released a factor that upregulates the expression of adhesion molecules on vascular EC.The supernatant of CEM (CEM-SUP) increased the expression of both ICAM-1 and ELAM-1 in time- and dose-dependent manners as shown by cell enzyme-linked immunoadsobent assay (ELISA). In contrast, the induction of VCAM-1 on EC with CEM-SUP was relatively weak. No reactivity for interleukin-lalpha, interleukin-1 beta, interferon-gamma, or tumor necrosis factor alpha, which are known to augment ICAM-1 expression, was detected in CEM-SUP by ELISA.In reverse transcriptase polymerase chain reaction (RT-PCR) assay, CEM expressed a minimum amount of tumor necrosis factor alpha mRNA but absolutely no interleukin 1 beta and interferon gamma mRNA.In addition, anttibodies to cytokines did not inhibit the upregulatory effect of CEM-SUP.Semipurified CEM-SUP further increased the cellular binding between CEM cells and EC in vitro. This factor was stabel to heat (65ﾟC,30 min) and labile to acid (pH2). Gel filtration and chromatofocusing estimated its molecular weight at 50 with an isoelectric point of ph 7.2. Produciton of this factor might contribute the invasive charcter of cEM through upregulation of adhesion molecules on EC.