Gruss H J, Scott C, Rollins B J, Brach M A, Herrmann F
Department of Internal Medicine III, University of Ulm Medical Center, Germany.
J Immunol. 1996 Jul 15;157(2):851-7.
Expression of IL-2R was examined on human fibroblasts isolated from different tissues. By specific binding assay it is shown that [125I]IL-2 bound to subconfluent adult bone marrow and embryonic skin and lung fibroblasts. The presence of binding sites for IL-2 was also confirmed by immunofluorescence and flow cytometry analysis using mAbs specific for the p55 IL-2R alpha (anti-CD25), p75 IL-2R beta, and p64 IL-2R gamma subunits. Fibroblasts also constitutively transcribed the genes coding for IL-2R alpha and IL-2R beta and accumulated their respective mRNAs but failed to exhibit the IL-2R gamma-chain on the mRNA and protein level. Although addition of IL-2 to fibroblast cultures did not significantly alter growth kinetics of these cells, the IL-2R complex displayed by fibroblasts appeared to be functional in that addition of IL-2 to these cells led to enhanced expression of the JE gene coding for the monocyte chemoattractant protein-1 (MCP-1). Enhancement of fibroblast MCP-1/JE gene expression by IL-2 appeared to result from delayed MCP-1/JE mRNA decay rather than as a consequence of an acceleration of the MCP-1/JE gene transcription rate. IL-2 had, however, no effect on the expression of other cytokine genes including IL-1, IL-5, IL-6, IL-7, IL-8, IL-9, granulocyte-macrophage-CSF, macrophage-CSF or TNF. These observations suggest that the range of cellular targets of IL-2 is broader than originally appreciated. IL-2 may thus serve to integrate fibroblasts and monocytes into a coordinated response of the connective tissue initiated by T lymphocytes.
对从不同组织分离出的人成纤维细胞上的白细胞介素-2受体(IL-2R)表达情况进行了检测。通过特异性结合试验表明,[125I]IL-2可与亚汇合状态的成人骨髓、胚胎皮肤和肺成纤维细胞结合。使用针对p55 IL-2Rα(抗CD25)、p75 IL-2Rβ和p64 IL-2Rγ亚基的单克隆抗体进行免疫荧光和流式细胞术分析,也证实了存在IL-2的结合位点。成纤维细胞还组成性地转录编码IL-2Rα和IL-2Rβ的基因,并积累各自的信使核糖核酸(mRNA),但在mRNA和蛋白质水平上均未表现出IL-2Rγ链。尽管向成纤维细胞培养物中添加IL-2并未显著改变这些细胞的生长动力学,但成纤维细胞所展示的IL-2R复合物似乎具有功能,因为向这些细胞中添加IL-2会导致编码单核细胞趋化蛋白-1(MCP-1)的JE基因表达增强。IL-2对成纤维细胞MCP-1/JE基因表达的增强作用似乎是由于MCP-1/JE mRNA降解延迟,而不是MCP-1/JE基因转录速率加快的结果。然而,IL-2对包括白细胞介素-1、白细胞介素-5、白细胞介素-6、白细胞介素-7、白细胞介素-8、白细胞介素-9、粒细胞-巨噬细胞集落刺激因子、巨噬细胞集落刺激因子或肿瘤坏死因子在内的其他细胞因子基因的表达没有影响。这些观察结果表明,IL-2的细胞靶标范围比最初认为的更广泛。因此,IL-2可能有助于将成纤维细胞和单核细胞整合到由T淋巴细胞引发的结缔组织协调反应中。