Tomokuni A, Otsuki T, Isozaki Y, Kita S, Ueki H, Kusaka M, Kishimoto T, Ueki A
Department of Hygiene, Kawasaki Medical School, Kurashiki, Okayama, Japan.
Clin Exp Immunol. 1999 Dec;118(3):441-4. doi: 10.1046/j.1365-2249.1999.01083.x.
Certain patients with silicosis have been reported to exhibit immunological abnormalities such as the appearance of antinuclear antibodies and the occurrence of autoimmune diseases. Fas ligand (FasL) is a type II membrane protein which induces apoptosis by binding to its membrane receptor, Fas. FasL is converted to a soluble form by a metalloproteinase-like enzyme. We have already found serum soluble Fas (sFas) levels in silicosis patients as well as in patients with systemic lupus erythematosus (SLE) to be significantly higher than those in healthy volunteers. To examine further the role of the Fas/FasL system in silica-induced immunological abnormalities, we investigated serum soluble FasL (sFasL) levels in silicosis patients with no clinical symptoms of autoimmune diseases, using ELISA for sFasL. Although the serum sFasL levels in patients with SLE were significantly higher than those in healthy volunteers and showed a slight positive correlation with serum sFas levels, those in silicosis patients exhibited no significant difference from those in healthy volunteers, and there was no correlation with serum sFas levels. However, sFasL levels were elevated in silicosis patients with slight dyspnoea or normal PCO2 among various clinical parameters of silicosis. It may be speculated that the immunological disturbances presented by the abnormalities of apoptosis-related molecules in silicosis patients do not occur with a similar degree of respiratory involvement. Further studies are required to clarify which kinds of factors are involved in silicosis patients who exhibit immunological abnormalities.
据报道,某些矽肺患者会出现免疫异常,如抗核抗体的出现和自身免疫性疾病的发生。Fas配体(FasL)是一种II型膜蛋白,通过与其膜受体Fas结合诱导细胞凋亡。FasL可被一种类金属蛋白酶转化为可溶性形式。我们已经发现,矽肺患者以及系统性红斑狼疮(SLE)患者的血清可溶性Fas(sFas)水平显著高于健康志愿者。为了进一步研究Fas/FasL系统在二氧化硅诱导的免疫异常中的作用,我们使用sFasL的ELISA法,对无自身免疫性疾病临床症状的矽肺患者的血清可溶性FasL(sFasL)水平进行了研究。虽然SLE患者的血清sFasL水平显著高于健康志愿者,且与血清sFas水平呈轻微正相关,但矽肺患者的血清sFasL水平与健康志愿者相比无显著差异,且与血清sFas水平无相关性。然而,在矽肺的各种临床参数中,轻度呼吸困难或正常PCO2的矽肺患者的sFasL水平升高。可以推测,矽肺患者中凋亡相关分子异常所呈现的免疫紊乱在呼吸受累程度相似时不会发生。需要进一步研究以阐明哪些因素与出现免疫异常的矽肺患者有关。