COMPROMISED KUPFFER CELLS COULD LEAD TO TCE-MEDIATED SLE-LIKE DISEASE

Shakuntala Kondraganti, M.D.¹, P.J. Boor, M.D.², M.F. Khan, Ph.D. ², R. Konig, Ph.D.³, B.S. Kaphalia, Ph.D.²,G.A.S.Ansari, Ph.D. ^1,2

Department of Biochemistry and Molecular Biology¹, Department of Pathology², Department of Microbiology and Immunology³, UTMB

Background: Trichloroethene (TCE) is ubiquitous in the environment; exposure to TCE has been shown to cause autoimmune diseases similar to systemic sclerosis, systemic lupus erythematosus, and fascitis. Previous studies in our lab have shown TCE induced/accelerated autoimmune responses similar to SLE in female MRL+/+ mice. Hypothesis: SLE-like autoimmune responses in TCE treated female MRL+/+ mice may be related to delayed clearance of apoptotic bodies due to dysfunctional Kupffer cells. Methods: Female MRL+/+ mice from Jackson Laboratory were treated with 0.5mg/ml of TCE in drinking water for 24, 36 and 48 weeks. Liver sections were stained with H & E, TUNEL for apoptsis, and Immunohistochemistry (Peroxidase) for Kupffer cells. Results: Diffuse lymphocytic infiltration was observed at 48 weeks compared to 24 and 36 weeks of TCE treatment. Two-fold increase in apoptosis was observed at 24 weeks with decreased number of macrophages at 48 weeks. Conclusions: Kupffer cell function is compromised in mice treated with TCE for 48 weeks compared to 24 and 36 weeks; this may result in delayed clearance of apoptotic bodies.