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肝纤维化形成的免疫机制。慢性活动性肝炎中T淋巴细胞介导的成纤维细胞胶原生成刺激。

Immune mechanisms for hepatic fibrogenesis. T-lymphocyte-mediated stimulation of fibroblast collagen production in chronic active hepatitis.

作者信息

Casini A, Ricci O E, Paoletti F, Surrenti C

出版信息

Liver. 1985 Jun;5(3):134-41. doi: 10.1111/j.1600-0676.1985.tb00228.x.

DOI:10.1111/j.1600-0676.1985.tb00228.x
PMID:3876501
Abstract

Lymphocytes can produce soluble factors capable of enhancing fibroblast proliferation and collagen synthesis. T-lymphocytes, adherent cells and undifferentiated peripheral blood mononuclear cells from patients with HBsAg-positive chronic active hepatitis and from HBsAg healthy carriers were triggered with purified HBsAg and tested for their ability to enhance collagen production by human dermal fibroblast cultures. Purified HBsAg did not induce any proliferative response in the mononuclear cell cultures. Addition of patient T-lymphocyte supernates to monolayers of fibroblast consistently resulted in a significant enhancement of collagen production. On the contrary, supernates harvested from adherent cell cultures did not demonstrate any stimulatory activity. We therefore assumed that the observed enhancement of collagen production was probably the result of lymphokine(s) produced by T-lymphocytes. This fibrogenic factor (or factors), which is released by T-cells independently of the presence in vitro of HBsAg, is stable at -80 degrees C, not dialyzable and, by Sephadex G-100 gel filtration, is present in a fraction which collects substances of a molecular weight between 50 000 and 100 000. Mononuclear cell supernates from HBsAg healthy carriers did not influence fibroblast collagen accumulation. These data emphasize the possible role that lymphokines may play in the pathogenesis of fibrosis during the natural history of chronic liver disease.

摘要

淋巴细胞能够产生可增强成纤维细胞增殖和胶原蛋白合成的可溶性因子。用纯化的乙肝表面抗原(HBsAg)刺激乙肝表面抗原阳性慢性活动性肝炎患者及乙肝表面抗原健康携带者的T淋巴细胞、贴壁细胞和未分化的外周血单核细胞,并检测它们增强人皮肤成纤维细胞培养物中胶原蛋白产生的能力。纯化的乙肝表面抗原在单核细胞培养物中未诱导任何增殖反应。将患者T淋巴细胞培养上清液添加到成纤维细胞单层中,始终会导致胶原蛋白产生显著增强。相反,从贴壁细胞培养物中收获的上清液未显示任何刺激活性。因此,我们推测观察到的胶原蛋白产生增强可能是T淋巴细胞产生的淋巴因子的结果。这种由T细胞释放的促纤维化因子(或多种因子),在体外独立于乙肝表面抗原的存在而释放,在-80℃稳定,不可透析,通过Sephadex G-100凝胶过滤,存在于一个收集分子量在50000至100000之间物质的组分中。乙肝表面抗原健康携带者的单核细胞培养上清液不影响成纤维细胞胶原蛋白的积累。这些数据强调了淋巴因子在慢性肝病自然病程中纤维化发病机制中可能发挥的作用。

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