title: Induction of anti-metallothionein antibody and mercury treatment decreases bone mineral density in mice.
abstract: Mercuric chloride (HgCl2) is an industrial agent with toxic effects on the immune system, kidney, lung, and nervous tissue, but little is known about its effect on bone. Metallothionein (MT) is a cysteine-rich metal-binding protein that exerts cytoprotective effects against heavy metal toxins. It has been reported that the susceptibility of renal and pulmonary toxicity of mercury was markedly enhanced in MT-null mice compared to control mice. However, there is no report about the effects of anti-metallothionein (anti-MT) Ab induction on mercury toxicity. We investigated the effect of anti-MT Ab induction on mercury-induced bone injury. BALB/c mice were injected with MT (10 microg/mouse ic) five times to induce anti-MT Ab and then treated with HgCl2 (1 mg/kg sc) three times per week for 3 weeks. MT immunization plus HgCl2 treatment dramatically decreased bone mineral density (BMD), and the humoral bone formation indices, alkaline phosphatase (ALP) activity and osteocalcin. MT immunization or HgCl2 treatment alone did not affect either BMD or serum ALP activity and osteocalcin levels. MT immunization impeded HgCl2-induced increase of MT expression in the liver and led to an increase of mercury in serum and the liver but a decrease in the kidney. Furthermore, serum titers of IgE and IgG1 were significantly elevated in the MT-immunized plus HgCl2 treatment group compared with those in the HgCl2 treatment group. Similar results were also observed in splenic secretions of IL-4 and IL-10 based on anti-CD3 Ab stimulation. Taken together, our results indicate that anti-MT Ab induction causes mercury-induced bone injury in BALB/c mice and also enhances mercury-related immune disorders.
authors.affiliation: Department of Geriatric Medicine, University of Tokyo, Tokyo, 113-8655, Japan.
authors.forename: Guang-Bi
authors.initials: GB
authors.lastname: Jin
authors.forename: Satoshi
authors.initials: S
authors.lastname: Inoue
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Urano
authors.forename: Shigefumi
authors.initials: S
authors.lastname: Cho
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Ouchi
authors.forename: Jong-Chol
authors.initials: JC
authors.lastname: Cyong
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D015519:Bone Density / Q000187:drug effects* / Q000276:immunology; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000097:blood; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D016753:Interleukin-10 / Q000096:biosynthesis / Q000097:blood; D015847:Interleukin-4 / Q000096:biosynthesis / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D008627:Mercuric Chloride / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D008668:Metallothionein / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D015675:Osteocalcin / Q000097:blood; D011897:Random Allocation; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D007074:Immunoglobulin G; D015675:Osteocalcin; D016753:Interleukin-10; D015847:Interleukin-4; D007073:Immunoglobulin E; D008627:Mercuric Chloride; D008668:Metallothionein; D000469:Alkaline Phosphatase