Differential Immune Responses to Albumin Adducts of Reactive Intermediates of Trichloroethene in MRL+/+ Mice

Overview

Journal Toxicol Appl Pharmacol

Specialties Pharmacology
Toxicology

Date 2007 Mar 23

PMID 17376499

Citations 7

Authors

Ping Cai

Rolf Konig

M Firoze Khan

Bhupendra S Kaphalia

G A S Ansari

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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References

Forkert P, Millen B, Lash L, Putt D, Ghanayem B . Pulmonary bronchiolar cytotoxicity and formation of dichloroacetyl lysine protein adducts in mice treated with trichloroethylene. J Pharmacol Exp Ther. 2005; 316(2):520-9. DOI: 10.1124/jpet.105.093062. View

Lockey J, Kelly C, Cannon G, Colby T, Aldrich V, Livingston G . Progressive systemic sclerosis associated with exposure to trichloroethylene. J Occup Med. 1987; 29(6):493-6. View

Fay R, Mumtaz M . Development of a priority list of chemical mixtures occurring at 1188 hazardous waste sites, using the HazDat database. Food Chem Toxicol. 1996; 34(11-12):1163-5. DOI: 10.1016/s0278-6915(97)00090-2. View

Cai P, Konig R, Khan M, Qiu S, Kaphalia B, Ansari G . Autoimmune response in MRL+/+ mice following treatment with dichloroacetyl chloride or dichloroacetic anhydride. Toxicol Appl Pharmacol. 2006; 216(2):248-55. DOI: 10.1016/j.taap.2006.05.010. View

Giver C, Wong R, Moore 2nd D, Pallavicini M . Dermal benzene and trichloroethylene induce aneuploidy in immature hematopoietic subpopulations in vivo. Environ Mol Mutagen. 2001; 37(3):185-94. DOI: 10.1002/em.1027. View

Griffin J, Gilbert K, Pumford N . Inhibition of CYP2E1 reverses CD4+ T-cell alterations in trichloroethylene-treated MRL+/+ mice. Toxicol Sci. 2000; 54(2):384-9. DOI: 10.1093/toxsci/54.2.384. View

REINL W . [Scleroderma caused by trichloroethylene effects]. Zentralbl Arbeitsmed. 1957; 7(3):58-60. View

Finkelman F, Katona I, Mosmann T, Coffman R . IFN-gamma regulates the isotypes of Ig secreted during in vivo humoral immune responses. J Immunol. 1988; 140(4):1022-7. View

Cai H, Guengerich F . Acylation of protein lysines by trichloroethylene oxide. Chem Res Toxicol. 2000; 13(5):327-35. DOI: 10.1021/tx000003p. View

10.

Palmer J, Robe A, Burt A, Kirby J, Jones D . Covalent modification as a mechanism for the breakdown of immune tolerance to pyruvate dehydrogenase complex in the mouse. Hepatology. 2004; 39(6):1583-92. DOI: 10.1002/hep.20248. View

11.

Khan M, Kaphalia B, Prabhakar B, Kanz M, Ansari G . Trichloroethene-induced autoimmune response in female MRL +/+ mice. Toxicol Appl Pharmacol. 1995; 134(1):155-60. DOI: 10.1006/taap.1995.1179. View

12.

ISAGER H . Scleroderma after occupational exposure to trichlorethylene and trichlorethane. Acta Derm Venereol. 1987; 67(3):263-4. View

13.

Hatch G, Boykin E, Graham J, Lewtas J, Pott F, Loud K . Inhalable particles and pulmonary host defense: in vivo and in vitro effects of ambient air and combustion particles. Environ Res. 1985; 36(1):67-80. DOI: 10.1016/0013-9351(85)90008-8. View

14.

Goon A, Lee L, Tay Y, Yosipovitch G, Ng S, Giam Y . A case of trichloroethylene hypersensitivity syndrome. Arch Dermatol. 2001; 137(3):274-6. View

15.

Singh V, Mehrotra S, Agarwal S . The paradigm of Th1 and Th2 cytokines: its relevance to autoimmunity and allergy. Immunol Res. 1999; 20(2):147-61. DOI: 10.1007/BF02786470. View

16.

Griffin J, Gilbert K, Lamps L, Pumford N . CD4(+) T-cell activation and induction of autoimmune hepatitis following trichloroethylene treatment in MRL+/+ mice. Toxicol Sci. 2000; 57(2):345-52. DOI: 10.1093/toxsci/57.2.345. View

17.

Bossie A, Vitetta E . IFN-gamma enhances secretion of IgG2a from IgG2a-committed LPS-stimulated murine B cells: implications for the role of IFN-gamma in class switching. Cell Immunol. 1991; 135(1):95-104. DOI: 10.1016/0008-8749(91)90257-c. View

18.

Mazzullo M, Bartoli S, Bonora B, Colacci A, Lattanzi G, Niero A . In vivo and in vitro interaction of trichloroethylene with macromolecules from various organs of rat and mouse. Res Commun Chem Pathol Pharmacol. 1992; 76(2):192-208. View

19.

Bolt H, Filser J . Irreversible binding of chlorinated ethylenes to macromolecules. Environ Health Perspect. 1977; 21:107-12. PMC: 1475349. DOI: 10.1289/ehp.7721107. View

20.

Saihan E, Burton J, Heaton K . A new syndrome with pigmentation, scleroderma, gynaecomastia, Raynaud's phenomenon and peripheral neuropathy. Br J Dermatol. 1978; 99(4):437-40. DOI: 10.1111/j.1365-2133.1978.tb06184.x. View