TY - JOUR
T1 - Differential immune responses to albumin adducts of reactive intermediates of trichloroethene in MRL+/+ mice
AU - Cai, Ping
AU - König, Rolf
AU - Khan, M. Firoze
AU - Kaphalia, Bhupendra S.
AU - Ansari, G. A.S.
N1 - Funding Information:
This publication was made possible by grant ES11584 from the National Institute of Environment Health Sciences (NIEHS), and its content are solely the responsibility of the authors and do not necessarily represent the views of the NIH or NIEHS. We gratefully acknowledge the Organic Synthesis Core at UTMB for the preparation of protein adducts and the Biomolecular Resource Facility at UTMB for their characterization by MALDI–TOF. Core facility support by NIEHS center grant (P30ES06676) is gratefully acknowledged.
PY - 2007/5/1
Y1 - 2007/5/1
N2 - 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 IgG1, IgG2a, and IgG2b, with IgG1 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.
AB - 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 IgG1, IgG2a, and IgG2b, with IgG1 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.
KW - Albumin adducts
KW - Autoimmune hepatitis
KW - Autoimmunity
KW - Trichloroethene (TCE)
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U2 - 10.1016/j.taap.2007.01.020
DO - 10.1016/j.taap.2007.01.020
M3 - Article
C2 - 17376499
AN - SCOPUS:34247281956
SN - 0041-008X
VL - 220
SP - 278
EP - 283
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
IS - 3
ER -