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. 2003 Aug;12(4):209–214. doi: 10.1080/09629350310001599648

Expression of Fas antigen and Fas ligand in bronchoalveolar lavage from silicosis patients.

Agnès Hamzaoui 1, Jamel Ammar 1, Hédia Graïri 1, Kamel Hamzaoui 1
PMCID: PMC1781620  PMID: 14514471

Abstract

OBJECTIVE: To understand the role of apoptosis through Fas/Fas ligand (FasL) interaction in the pathogenesis of silicosis, we examined the expression of Fas antigen, FasL and apoptosis in bronchoalveolar lavage fluid lymphocytes obtained from patients with silicosis. MATERIALS AND METHODS: Ten patients with silicosis, and 10 healthy controls were studied. Non-adherent cells were separated and analysed by cytometry for the expression of Fas antigen, FasL, and the co-expression of Fas/FasL. By double staining, we studied the FasL expression on CD4, CD8, CD56 and CD45RO-positive cells. DNA fragmentation was investigated by the terminal deoxy(d) UTP nick end labelling (TUNEL) method. RESULTS: We have found Fas and FasL expression in silicosis patients to be significantly higher than those in healthy controls. Interestingly, 6-18% of lymphocytes from silicosis patients co-expressed Fas and FasL. In silicosis patients, FasL was highly expressed on CD4+, CD56+ and CD45RO+ bronchoalveolar lavage cells. Fas antigen expressing cells showed DNA fragmentation characteristic for apoptosis. CONCLUSION: FasL was significantly expressed on cytotoxic effector and memory cells. The Fas/FasL system is implicated in the inflammatory process observed in silicosis patients.

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Selected References

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  1. Adachi M., Watanabe-Fukunaga R., Nagata S. Aberrant transcription caused by the insertion of an early transposable element in an intron of the Fas antigen gene of lpr mice. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1756–1760. doi: 10.1073/pnas.90.5.1756. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Asahara H., Hasumuna T., Kobata T., Yagita H., Okumura K., Inoue H., Gay S., Sumida T., Nishioka K. Expression of Fas antigen and Fas ligand in the rheumatoid synovial tissue. Clin Immunol Immunopathol. 1996 Oct;81(1):27–34. doi: 10.1006/clin.1996.0153. [DOI] [PubMed] [Google Scholar]
  3. Brinkmann V., Kristofic C. Regulation by corticosteroids of Th1 and Th2 cytokine production in human CD4+ effector T cells generated from CD45RO- and CD45RO+ subsets. J Immunol. 1995 Oct 1;155(7):3322–3328. [PubMed] [Google Scholar]
  4. Cheng J., Zhou T., Liu C., Shapiro J. P., Brauer M. J., Kiefer M. C., Barr P. J., Mountz J. D. Protection from Fas-mediated apoptosis by a soluble form of the Fas molecule. Science. 1994 Mar 25;263(5154):1759–1762. doi: 10.1126/science.7510905. [DOI] [PubMed] [Google Scholar]
  5. D'Império Lima M. R., Alvarez J. M., Furtado G. C., Kipnis T. L., Coutinho A., Minóprio P. Ig-isotype patterns of primary and secondary B cell responses to Plasmodium chabaudi chabaudi correlate with IFN-gamma and IL-4 cytokine production with CD45RB expression by CD4+ spleen cells. Scand J Immunol. 1996 Mar;43(3):263–270. doi: 10.1046/j.1365-3083.1996.d01-35.x. [DOI] [PubMed] [Google Scholar]
  6. Davis G. S., Pfeiffer L. M., Hemenway D. R. Interferon-gamma production by specific lung lymphocyte phenotypes in silicosis in mice. Am J Respir Cell Mol Biol. 2000 Apr;22(4):491–501. doi: 10.1165/ajrcmb.22.4.3599. [DOI] [PubMed] [Google Scholar]
  7. Firestein G. S., Yeo M., Zvaifler N. J. Apoptosis in rheumatoid arthritis synovium. J Clin Invest. 1995 Sep;96(3):1631–1638. doi: 10.1172/JCI118202. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Garn H., Friedetzky A., Davis G. S., Hemenway D. R., Gemsa D. T-lymphocyte activation in the enlarged thoracic lymph nodes of rats with silicosis. Am J Respir Cell Mol Biol. 1997 Mar;16(3):309–316. doi: 10.1165/ajrcmb.16.3.9070616. [DOI] [PubMed] [Google Scholar]
  9. Gavrieli Y., Sherman Y., Ben-Sasson S. A. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol. 1992 Nov;119(3):493–501. doi: 10.1083/jcb.119.3.493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hamzaoui K., Hamzaoui A., Hentati F., Kahan A., Ayed K., Chabbou A., Ben Hamida M., Hamza M. Phenotype and functional profile of T cells expressing gamma delta receptor from patients with active Behçet's disease. J Rheumatol. 1994 Dec;21(12):2301–2306. [PubMed] [Google Scholar]
  11. Hamzaoui K., Hamzaoui A., Zakraoui L., Chabbou A. Levels of soluble Fas/APO-1 in patients with Behçet's disease. Mediators Inflamm. 1998;7(2):111–114. doi: 10.1080/09629359891261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kinoshita T., Imamura J., Nagai H., Shimotohno K. Quantification of gene expression over a wide range by the polymerase chain reaction. Anal Biochem. 1992 Nov 1;206(2):231–235. doi: 10.1016/0003-2697(92)90358-e. [DOI] [PubMed] [Google Scholar]
  13. Kinugawa K., Ueki A., Yamaguchi M., Watanabe Y., Kawakami Y., Hyodoh F., Tsushima H. Activation of human CD4+CD45RA+ T cells by chrysotile asbestos in vitro. Cancer Lett. 1992 Sep 30;66(2):99–106. doi: 10.1016/0304-3835(92)90221-g. [DOI] [PubMed] [Google Scholar]
  14. Kägi D., Vignaux F., Ledermann B., Bürki K., Depraetere V., Nagata S., Hengartner H., Golstein P. Fas and perforin pathways as major mechanisms of T cell-mediated cytotoxicity. Science. 1994 Jul 22;265(5171):528–530. doi: 10.1126/science.7518614. [DOI] [PubMed] [Google Scholar]
  15. Lanzillo J. J. Chemiluminescent nucleic acid detection with digoxigenin-labeled probes: a model system with probes for angiotensin converting enzyme which detect less than one attomole of target DNA. Anal Biochem. 1991 Apr;194(1):45–53. doi: 10.1016/0003-2697(91)90149-n. [DOI] [PubMed] [Google Scholar]
  16. Levesque M. C., Haynes B. F. Activated T lymphocytes regulate hyaluronan binding to monocyte CD44 via production of IL-2 and IFN-gamma. J Immunol. 2001 Jan 1;166(1):188–196. doi: 10.4049/jimmunol.166.1.188. [DOI] [PubMed] [Google Scholar]
  17. Nakajima T., Aono H., Hasunuma T., Yamamoto K., Shirai T., Hirohata K., Nishioka K. Apoptosis and functional Fas antigen in rheumatoid arthritis synoviocytes. Arthritis Rheum. 1995 Apr;38(4):485–491. doi: 10.1002/art.1780380405. [DOI] [PubMed] [Google Scholar]
  18. Nakajima T., Aono H., Hasunuma T., Yamamoto K., Shirai T., Hirohata K., Nishioka K. Apoptosis and functional Fas antigen in rheumatoid arthritis synoviocytes. Arthritis Rheum. 1995 Apr;38(4):485–491. doi: 10.1002/art.1780380405. [DOI] [PubMed] [Google Scholar]
  19. Oka S., Mori N., Matsuyama S., Takamori Y., Kubo K. Presence of B220 within thymocytes and its expression on the cell surface during apoptosis. Immunology. 2000 Aug;100(4):417–423. doi: 10.1046/j.1365-2567.2000.00063.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Otsuki T., Sakaguchi H., Tomokuni A., Aikoh T., Matsuki T., Kawakami Y., Kusaka M., Ueki H., Kita S., Ueki A. Soluble Fas mRNA is dominantly expressed in cases with silicosis. Immunology. 1998 Jun;94(2):258–262. doi: 10.1046/j.1365-2567.1998.00509.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Renno T., Attinger A., Rimoldi D., Hahne M., Tschopp J., MacDonald H. R. Expression of B220 on activated T cell blasts precedes apoptosis. Eur J Immunol. 1998 Feb;28(2):540–547. doi: 10.1002/(SICI)1521-4141(199802)28:02<540::AID-IMMU540>3.0.CO;2-Y. [DOI] [PubMed] [Google Scholar]
  22. Robinson A. T., Miller N., Alexander D. R. CD3 antigen-mediated calcium signals and protein kinase C activation are higher in CD45R0+ than in CD45RA+ human T lymphocyte subsets. Eur J Immunol. 1993 Jan;23(1):61–68. doi: 10.1002/eji.1830230111. [DOI] [PubMed] [Google Scholar]
  23. Sakata-Kaneko S., Wakatsuki Y., Matsunaga Y., Usui T., Kita T. Altered Th1/Th2 commitment in human CD4+ T cells with ageing. Clin Exp Immunol. 2000 May;120(2):267–273. doi: 10.1046/j.1365-2249.2000.01224.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Smalley D. L., Shanklin D. R., Hall M. F. Monocyte-dependent stimulation of human T cells by silicon dioxide. Pathobiology. 1998;66(6):302–305. doi: 10.1159/000028037. [DOI] [PubMed] [Google Scholar]
  25. Takahashi T., Tanaka M., Brannan C. I., Jenkins N. A., Copeland N. G., Suda T., Nagata S. Generalized lymphoproliferative disease in mice, caused by a point mutation in the Fas ligand. Cell. 1994 Mar 25;76(6):969–976. doi: 10.1016/0092-8674(94)90375-1. [DOI] [PubMed] [Google Scholar]
  26. Tomokuni A., Aikoh T., Matsuki T., Isozaki Y., Otsuki T., Kita S., Ueki H., Kusaka M., Kishimoto T., Ueki A. Elevated soluble Fas/APO-1 (CD95) levels in silicosis patients without clinical symptoms of autoimmune diseases or malignant tumours. Clin Exp Immunol. 1997 Nov;110(2):303–309. doi: 10.1111/j.1365-2249.1997.tb08332.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Tomokuni A., Otsuki T., Isozaki Y., Kita S., Ueki H., Kusaka M., Kishimoto T., Ueki A. Serum levels of soluble Fas ligand in patients with silicosis. Clin Exp Immunol. 1999 Dec;118(3):441–444. doi: 10.1046/j.1365-2249.1999.01083.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Ueki A., Isozaki Y., Tomokuni A., Hatayama T., Ueki H., Kusaka M., Shiwa M., Arikuni H., Takeshita T., Morimoto K. Intramolecular epitope spreading among anti-caspase-8 autoantibodies in patients with silicosis, systemic sclerosis and systemic lupus erythematosus, as well as in healthy individuals. Clin Exp Immunol. 2002 Sep;129(3):556–561. doi: 10.1046/j.1365-2249.2002.01939.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Ueki A., Yamaguchi M., Ueki H., Watanabe Y., Ohsawa G., Kinugawa K., Kawakami Y., Hyodoh F. Polyclonal human T-cell activation by silicate in vitro. Immunology. 1994 Jun;82(2):332–335. [PMC free article] [PubMed] [Google Scholar]

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