title: Evaluation of immunotoxic and immunodisruptive effects of inorganic arsenite on human monocytes/macrophages.
abstract: A trivalent inorganic arsenic, arsenite, has been causing chronic inflammation in humans through the consumption of contaminated well water. The total peripheral blood arsenic concentrations of chronic arsenic-exposed patients, who had inflammatory-like immune responses, are less than 1 microM, thus, nM concentrations may be very important regarding the chronic inflammatory effects by arsenite. However, there are few reports about the biological effects of low concentrations of arsenite in mammalian cells, especially in normal immune effector cells. In this study, we examined whether arsenite has any biological and/or toxicological effects on the differentiation of human peripheral blood monocytes into macrophages using the colony-stimulating factor (CSF) in vitro compared with that of other metallic compounds, and found that arsenite sensitively inhibited the CSF-induced in vitro maturation of monocytes into macrophages at nM levels, and it also induced small, nonadhesive and CD14-positive abnormal macrophage generation from monocytes with granulocyte-macrophage CSF (GM-CSF) at 50-500 nM without cell death. The addition of other metallic compounds, including chromium, selenium, mercury, cadmium, nickel, copper, zinc, cobalt, manganese and other human pentavalent arsenic metabolites, such as inorganic arsenate, monomethylarsonic acid and dimethylarsinic acid, could not induce the same abnormal cell generation from monocytes with CSFs at any concentration and any additional time schedules; they showed only simple cytolethality in monocytes and macrophages at any concentration and any additional time schedules; they showed only simple cytolethality in monocytes and macrophages at n-mM levels accompanied by cell death. This work may have implications in the arsenic-induced chronic inflammation in humans.
authors.affiliation: Laboratory of Environmental Chemistry, School of Life Science, Tokyo University of Pharmacy and Life Science, Horinouchi 1432-1, Hachioji, Tokyo 192-0392, Japan. sakurai@ph.bunri-u.ac.jp
authors.forename: Teruaki
authors.initials: T
authors.lastname: Sakurai
authors.forename: Takami
authors.initials: T
authors.lastname: Ohta
authors.forename: Norifumi
authors.initials: N
authors.lastname: Tomita
authors.forename: Chikara
authors.initials: C
authors.lastname: Kojima
authors.forename: Yukie
authors.initials: Y
authors.lastname: Hariya
authors.forename: Ayumu
authors.initials: A
authors.lastname: Mizukami
authors.forename: Kitao
authors.initials: K
authors.lastname: Fujiwara
mesh_terms: D018053:Arsenites / Q000633:toxicity*; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D004785:Environmental Pollutants / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D000922:Immunotoxins; D018664:Interleukin-12 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D009569:Nitric Oxide / Q000378:metabolism; D010641:Phenotype; D017382:Reactive Oxygen Species / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D018053:Arsenites; D016207:Cytokines; D004785:Environmental Pollutants; D000922:Immunotoxins; D017382:Reactive Oxygen Species; D018664:Interleukin-12; D009569:Nitric Oxide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D005978:Glutathione; C015001:arsenite