title: Complement activation and liver impairment in trichloroethylene-sensitized BALB/c mice.
abstract: Our recent studies have shown that trichloroethylene (TCE) was able to induce multisystem injuries in the form of occupational medicamentosa-like dermatitis, including skin, kidney, and liver damages. However, the role of complement activation in the immune-mediated liver injury is not known. This study examined the role of complement activation in the liver injury in a mouse model of TCE-induced sensitization. Treatment of female BALB/c mice with TCE under specific dosing protocols resulted in skin inflammation and sensitization. Skin edema and erythema occurred in TCE-sensitized groups. Trichloroethylene sensitization produced liver histopathological lesions, increased serum alanine aminotransferase, aspartate transaminase activities, and the relative liver weight. The concentrations of serum complement components C3a-desArg, C5a-desArg, and C5b-9 were significantly increased in 24-hour, 48-hour, and 72-hour sensitization-positive groups treated with TCE and peaked in the 72-hour sensitization-positive group. Depositions of C3a, C5a, and C5b-9 into the liver tissue were also revealed by immunohistochemistry. Immunofluorescence further verified high C5b-9 expression in 24-hour, 48-hour, and 72-hour sensitization-positive groups in response to TCE treatment. Reverse transcription-polymerase chain reaction detected C3 messenger RNA expression in the liver, and this was significantly increased in 24-hour and 48-hour sensitization-positive groups with a transient reduction at 72 hours. These results provide the first experimental evidence that complement activation may play a key role in the generation and progression of immune-mediated hepatic injury by exposure to TCE.
authors.affiliation: Institute of Dermatology, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, PR China. Email: zqxing@yeah.net.
authors.forename: Jiaxiang
authors.initials: J
authors.lastname: Zhang
authors.forename: Wansheng
authors.initials: W
authors.lastname: Zha
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: Shuhai
authors.initials: S
authors.lastname: Xu
authors.forename: Junfeng
authors.initials: J
authors.lastname: Yu
authors.forename: Chengfan
authors.initials: C
authors.lastname: Zhou
authors.forename: Tong
authors.initials: T
authors.lastname: Shen
authors.forename: Changhao
authors.initials: C
authors.lastname: Wu
authors.forename: Qixing
authors.initials: Q
authors.lastname: Zhu
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology*; D003167:Complement Activation / Q000187:drug effects*; D015926:Complement C3a / Q000276:immunology; D015936:Complement C5a / Q000276:immunology; D015938:Complement Membrane Attack Complex / Q000276:immunology; D005260:Female; D006967:Hypersensitivity / Q000209:etiology / Q000276:immunology*; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D014241:Trichloroethylene / Q000633:toxicity*
chemical_list: D015938:Complement Membrane Attack Complex; D014241:Trichloroethylene; D015926:Complement C3a; D015936:Complement C5a; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: C3a; C5a; C5b-9; complement activation; liver injury; trichloroethylene