Otsuki T, Sakaguchi H, Tomokuni A, Aikoh T, Matsuki T, Kawakami Y, Kusaka M, Ueki H, Kita S, Ueki A
Department of Hygiene, Kawasaki Medical School, Okayama, Japan.
Immunology. 1998 Jun;94(2):258-62. doi: 10.1046/j.1365-2567.1998.00509.x.
Although it is well known that cases with silicosis exhibit various immunological abnormalities, the mechanisms involved in the occurrence of immuno-dysfunction or dysregulation induced by silica compounds have not yet been determined. Fas is a well-known cell surface molecule that is involved in the apoptosis pathway that belongs to the tumour necrosis factor-receptor family. Soluble Fas (sFas) is produced as an alternatively spliced product of the Fas gene and protects cells from apoptosis due to antagonization of the binding between membrane form of the Fas gene (mFas) and the Fas ligand. To determine the role of the Fas/Fas ligand system in silica-induced immunological abnormalities, we investigated Fas and Fas-ligand message expression levels using the multiplex reverse transcription-polymerase chain reaction (RT-PCR) method with peripheral blood mononuclear cells from silicosis cases with no clinical symptoms of autoimmune diseases. Although the relative expression levels of the Fas or Fas-ligand genes were not remarkably altered in these cases, we observed the sFas message was dominantly expressed compared with mFas expression. These results suggest that self-recognizing clones in cases with silicosis survive for decades, escaping the exclusion mechanisms induced by apoptosis. Then they cause the appearance of autoantibodies and the acquisition of autoimmune diseases sequentially.
尽管众所周知矽肺患者存在各种免疫异常，但二氧化硅化合物诱导免疫功能障碍或失调发生的机制尚未确定。Fas是一种著名的细胞表面分子，参与属于肿瘤坏死因子受体家族的凋亡途径。可溶性Fas（sFas）是Fas基因的可变剪接产物，由于拮抗Fas基因膜形式（mFas）与Fas配体之间的结合而保护细胞免于凋亡。为了确定Fas/Fas配体系统在二氧化硅诱导的免疫异常中的作用，我们使用多重逆转录聚合酶链反应（RT-PCR）方法，对无自身免疫性疾病临床症状的矽肺患者外周血单个核细胞进行检测，以研究Fas和Fas配体的信使表达水平。虽然在这些病例中Fas或Fas配体基因的相对表达水平没有明显改变，但我们观察到与mFas表达相比，sFas信使占主导表达。这些结果表明，矽肺患者的自身识别克隆存活数十年，逃避凋亡诱导的排除机制。然后它们依次导致自身抗体的出现和自身免疫性疾病的获得。
