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Induction of the cellular expression of   Induction of the cellular expression of... - PDF Document (3 M)
Title Induction of the cellular expression of human Ro autoantigens
Creator Zhu, Jianhui
Contributor Shuster, Joseph (advisor)
Date 1995
Abstract Ro autoantigens are intracellular ribonucleoproteins of unknown function. Autoantibodies to these antigens are detected frequently in patients with systemic lupus erythematosus (SLE) and involved in the pathogenesis of lupus skin lesions. Although the mechanisms responsible for the induction of these autoantibodies and immunologic tissue damage are unclear, one possibility is that Ro autoantigens are expressed on the cell surface and induce an immune response. Cell surface expression of Ro antigens has been reported previously following ultraviolet B (UVB) irradiation or estrogen stimulation of human keratinocytes. In this thesis, the effect of human cytomegalovirus (CMV) infection on the surface expression of Ro antigens and calreticulin on human fibroblasts and keratinocytes was investigated using a fixed cell enzyme-linked immunoassay (ELISA), immunofluorescence, flow cytometry (FACS) analysis and immunoblotting. CMV infection of cultured human fibroblast cells was found to increase the cell surface expression of calreticulin, but not 60kD/Ro antigen. However, CMV infection, in combination with UVB irradiation, synergistically induced the expression of 52kD/Ro antigen, but not 60kD/Ro or calreticulin, on the surface of these cells. This enhanced expression of 52kD/Ro autoantigen on CMV and UVB treated cells was significant and specific, compared with untreated cells, cells infected with CMV or irradiated with UVB only, and cells subjected to other treatments including low pH. These studies were then extended to human keratinocytes, which are relevant to the skin disease associated with the presence of anti-Ro antibodies in SLE. Human CMV was demonstrated to be capable of infecting keratinocytes in vitro and induced the surface expression of 60kD/Ro antigen, but not 52kD/Ro and calreticulin, on human keratinocytes. As there was no increase in total cellular expression of 60kD/Ro antigen after viral infection, 60kD/Ro antigen appears to be redistributed from the
Subject Biology, Cell.
Health Sciences, Immunology.
Degree Doctor of Philosophy
Department Division of Experimental Medicine.
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URL of this record http://digitool.Library.McGill.CA:80/R/-?func=dbin-jump-full&object_id=39900&silo_library=GEN01
PID 39900
Number of Downloads 10
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