Skip to main content
PMC home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1997 Nov;110(2):303–309. doi: 10.1111/j.1365-2249.1997.tb08332.x

Elevated soluble Fas/APO-1 (CD95) levels in silicosis patients without clinical symptoms of autoimmune diseases or malignant tumours

A TOMOKUNI *, T AIKOH *, T MATSUKI *, Y ISOZAKI *, T OTSUKI *, S KITA *, H UEKI †, M KUSAKA ‡, T KISHIMOTO §, A UEKI *
PMCID: PMC2265505  PMID: 9367417

Abstract

Soluble Fas (sFas) is produced as translation products of alternative mRNA splicing, and antagonizes the membranous Fas molecule in Fas/Fas ligand interactions. We investigated the serum sFas levels in 64 Japanese silicosis patients with no clinical symptoms of autoimmune diseases or malignant tumours, using ELISA for sFas. The serum sFas levels in the silicosis patients were significantly higher than those in healthy volunteers. Elevated serum sFas levels were also detected in patients with systemic lupus erythematosus but, unexpectedly, no difference was observed in sFas levels between progressive systemic sclerosis patients and healthy volunteers. On the other hand, there was no significant difference in the expression of Fas on peripheral blood lymphocytes between the patients with silicosis and age-matched healthy volunteers. These observations provided the first evidence that serum sFas levels are elevated in silicosis patients without clinical symptoms of autoimmune diseases or malignant tumours. It remains to be clarified whether patients with elevated sFas levels have a tendency to develop autoimmune diseases later, or whether some other distinct factor(s) is necessary to initiate the progression of autoimmune diseases.

Keywords: silicosis, soluble Fas, membranous Fas, apoptosis, autoimmunity

Full Text

The Full Text of this article is available as a PDF (471.3 KB).

References

  • 1.Cheng J, Zhou T, Liu C, et al. Protection from Fas-mediated apoptosis by a soluble form of the Fas molecule. Science. 1994;263:1759–62. doi: 10.1126/science.7510905. [DOI] [PubMed] [Google Scholar]
  • 2.Jodo S, Kobayashi N, Kayagaki N, et al. Serum levels of soluble Fas/ APO-1 (CD95) and its molecular structure in patients with systemic lupus erythematosus (SLE) and other autoimmune diseases. Clin Exp Immunol. 1997;107:89–95. doi: 10.1046/j.1365-2249.1997.d01-901.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Midis GP, Shen Y, Owen-Schaub LB. Elevated soluble Fas (sFas) levels in nonhaematopoietic human malignancy. Cancer Res. 1996;56:3870–4. [PubMed] [Google Scholar]
  • 4.Watanabe-Fukunaga R, Brannan CI, Copeland NG, et al. Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature. 1992;356:314–7. doi: 10.1038/356314a0. [DOI] [PubMed] [Google Scholar]
  • 5.Takahashi T, Tanaka M, Brannan CI, et al. Generalized lymphopro-liferative disease in mice, caused by a point mutation in the Fas ligand. Cell. 1994;76:969–76. doi: 10.1016/0092-8674(94)90375-1. [DOI] [PubMed] [Google Scholar]
  • 6.Rathmell JC, Cooke MP, Ho WY, et al. CD95 (Fas)-dependent elimination of self-reactive B cells upon interaction with CD4+ T cells. Nature. 1995;376:181–3. doi: 10.1038/376181a0. [DOI] [PubMed] [Google Scholar]
  • 7.Haustein UF, Ziegler V, Herrmann K, et al. Silica-induced scleroderma. J Am Acad Dermatol. 1990;22:444–8. doi: 10.1016/0190-9622(90)70062-m. [DOI] [PubMed] [Google Scholar]
  • 8.Sanchez-Roman J, Wichmann I, Salaberri J, et al. Multiple clinical and biological autoimmune manifestations in 50 workers after occupational exposure to silica. Ann Rheum Dis. 1993;52:534–8. doi: 10.1136/ard.52.7.534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Ueki A, Yamaguchi M, Ueki H, et al. Polyclonal human T-cell activation by silicate in vitro. Immunology. 1994;82:332–5. [PMC free article] [PubMed] [Google Scholar]
  • 10.Tapia FJ, Goihman YM, Caceres DG, et al. Leukocyte immunophenotypes in bronchoalveolar lavage fluid and peripheral blood of paracoccidioidomycosis, sarcoidosis and silicosis. Histol Histopathol. 1991;6:395–402. [PubMed] [Google Scholar]
  • 11.Miyawaki T, Uehara T, Nibu R, et al. Differential expression of apoptosis-related Fas antigen on lymphocyte subpopulations in human peripheral blood. J Immunol. 1992;11:3753–8. [PubMed] [Google Scholar]
  • 12.Knipping E, Krammer PH, Onel KB, et al. Levels of soluble Fas/APO-1/ CD95 in systemic lupus erythematosus and juvenile rheumatoid arthritis. Arthritis Rheum. 1995;38:1735–7. doi: 10.1002/art.1780381205. [DOI] [PubMed] [Google Scholar]
  • 13.Goel N, Ulrich DT, St Clair EW, et al. Lack of correlation between serum soluble Fas/APO-1 levels and autoimmune disease. Arthritis Rheum. 1995;38:1738–43. doi: 10.1002/art.1780381206. [DOI] [PubMed] [Google Scholar]
  • 14.Wu J, Wilson J, He J, et al. Fas ligand mutation in a patient with systemic lupus erythematosus and lymphoproliferative disease. J Clin Invest. 1996;98:1107–13. doi: 10.1172/JCI118892. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Seishima M, Takemura M, Saito K, et al. Highly sensitive ELISA for soluble Fas in serum: increased soluble Fas in the elderly. Clin Chem. 1996;42:1911–4. [PubMed] [Google Scholar]
  • 16.Bramwell B. Diffuse scleroderma: its frequency; its occurence in stonemasons; its treatment by fibrinolysin-elevations of temperature due to fibrinolysin injections. Ed Med J. 1914;12:387–401. [Google Scholar]
  • 17.Caplan A. Certain unusual radiological appearances in the chest of coal-miners suffering from rheumatoid arthritis. Thorax. 1953;8:29–37. doi: 10.1136/thx.8.1.29. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Erasmus LD. Scleroderma in gold-miners on the Witwatersrand with particular reference to pulmonary manifestations. S Afr J Lab Clin Med. 1958;3:209–31. [PubMed] [Google Scholar]
  • 19.Rodnan GP, Benedek TG, Medsger TA, Jr, et al. The association of progressive systemic sclerosis (scleroderma) with coal miners' pneumoconiosis and other forms of silicosis. Ann Intem Med. 1967;66:323–34. doi: 10.7326/0003-4819-66-2-323. [DOI] [PubMed] [Google Scholar]
  • 20.Uber CL, McReynolds RA. Immunotoxicology of silica. Crit Rev Toxicol. 1982;10:303–19. doi: 10.3109/10408448209003370. [DOI] [PubMed] [Google Scholar]
  • 21.Parkes WR. Fundamentals of pathogenesis and pathology. In: Parkes WR, editor. Occupational lung disorders. 2. London: Butterworths; 1982. pp. 54–88. [Google Scholar]
  • 22.Haslam LP. Basic immunology and immunopathology. In: Parkes WR, editor. Occupational lung disorders. 3. London: Butterworth Heine-mann; 1994. pp. 50–99. [Google Scholar]
  • 23.Rustin MHA, Bull HA, Ziegler V, et al. Silica-associated systemic sclerosis is clinically, serologically and immunologically indistinguishable from idiopathic systemic sclerosis. Br J Dermatol. 1990;123:725–34. doi: 10.1111/j.1365-2133.1990.tb04189.x. [DOI] [PubMed] [Google Scholar]
  • 24.Kinugawa K, Ueki A, Yamaguchi M, et al. Activation of human CD4+CD45RA+ T cells by chrysotile asbestos in vitro. Cancer Lett. 1992;66:99–106. doi: 10.1016/0304-3835(92)90221-g. [DOI] [PubMed] [Google Scholar]
  • 25.Kawabe Y, Ochi A. Programmed cell death and extrathymic reduction of V/38+ CD4+ T cells in mice tolerant to staphylococcus aureus enterotoxin B. Nature. 1991;349:245–8. doi: 10.1038/349245a0. [DOI] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES