Differential immune responses to albumin adducts of reactive intermediates of trichloroethene in MRL+/+ mice.
Trichloroethene (TCE) is an industrial degreasing solvent and widespread environmental contaminant. Exposure to TCE is associated with autoimmunity. The mode of action of TCE is via its oxidative metabolism, and most likely, immunotoxicity is mediated via haptenization of macromolecules and subsequent induction of immune responses. To better understand the role of protein haptenization through TCE metabolism, we immunized MRL+/+ mice with albumin adducts of various TCE reactive intermediates. Serum immunoglobulins and cytokine levels were measured to determine immune responses against haptenized albumin. We found antigen-specific IgG responses of the IgG subtypes IgG(1), IgG(2a), and IgG(2b), with IgG(1) predominating. Serum levels of G-CSF were increased in immunized mice, suggesting macrophage activation. Liver histology revealed lymphocyte infiltration in the lobules and the portal area following immunization with formyl-albumin. Our findings suggest that proteins haptenized by metabolites of TCE may act as neo-antigens that can induce humoral immune responses and T cell-mediated hepatitis.
Cai
Ping
P
Department of Pathology, University of Texas Medical Branch, Galveston TX 77555-0609, USA.
König
Rolf
R
Khan
M Firoze
MF
Kaphalia
Bhupendra S
BS
Ansari
G A S
GA
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood; D006241:Haptens / Q000737:chemistry / Q000276:immunology; D019693:Hepatitis, Autoimmune / Q000097:blood / Q000276:immunology; D022781:Hepatocytes / Q000276:immunology / Q000473:pathology; D007106:Immune Sera / Q000276:immunology; D007114:Immunization / Q000379:methods*; D007136:Immunoglobulins / Q000097:blood; D008099:Liver / Q000276:immunology / Q000473:pathology; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D051379:Mice; D019463:Mice, Inbred MRL lpr; D008970:Molecular Weight; D012709:Serum Albumin / Q000737:chemistry / Q000276:immunology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014241:Trichloroethylene / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D006241:Haptens; D007106:Immune Sera; D007136:Immunoglobulins; D012709:Serum Albumin; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; D014241:Trichloroethylene