title: Acute exposure to cadmium induces prolonged neutrophilia along with delayed induction of granulocyte colony-stimulating factor in the livers of mice.
abstract: Acute exposure to cadmium (Cd), a toxic heavy metal, causes systemic inflammation characterized by neutrophilia. To elucidate the mechanism of neutrophilia induced by Cd, we investigated the induction of granulocyte colony-stimulating factor (G-CSF), which regulates neutrophil production, in mice with acute Cd toxicity, and compared it with mice injected with lipopolysaccharide (LPS) as an inducer of general inflammatory responses. We injected BALB/c mice with Cd at 2.5 mg/kg i.p. or LPS at 0.5 mg/kg i.p. and sampled the peripheral blood and organs at time points up to 24 h. In Cd-treated mice, the peripheral neutrophil count increased steadily up to 24 h, whereas LPS-treated mice showed a more rapid increase with a peak at 12 h. The serum G-CSF level increased gradually to reach a plateau at 12-18 h in Cd-treated mice, but LPS-treated mice showed a marked increase, reaching a peak at 2-3 h. A gradual elevation of G-CSF mRNA expression up to 24 h was detected by real-time PCR in the livers of Cd-treated mice, but in LPS-treated mice its highest expression was observed in the liver with a rapid increase at 2 h. By in situ hybridization using G-CSF RNA probes, hepatic Kupffer cells were identified as G-CSF-producing cells in the liver. These results indicated that Cd has a characteristic effect of delayed induction of G-CSF in the liver, causing systemic inflammation accompanied by prolonged neutrophilia.
authors.affiliation: Department of Hygiene, Kitasato University School of Medicine, Sagamihara, Kanagawa, 010-8543, Japan. hhyogo@med.kitasato-u.ac.jp.|Division of Environmental Toxicology, Department of Pharmacology, School of Medicine, Jichi Medical University, Tochigi, 329-0498, Japan. hhyogo@med.kitasato-u.ac.jp.|Department of Hygiene, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan. hhyogo@med.kitasato-u.ac.jp.
authors.forename: Hyogo
authors.initials: H
authors.lastname: Horiguchi
authors.affiliation: Department of Hygiene, Kitasato University School of Medicine, Sagamihara, Kanagawa, 010-8543, Japan.|Division of Environmental Toxicology, Department of Pharmacology, School of Medicine, Jichi Medical University, Tochigi, 329-0498, Japan.
authors.forename: Etsuko
authors.initials: E
authors.lastname: Oguma
mesh_terms: D000208:Acute Disease; D000818:Animals; D002104:Cadmium / Q000097:blood / Q000378:metabolism / Q000633:toxicity; D002105:Cadmium Poisoning / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D004731:Endotoxins / Q000633:toxicity; D004785:Environmental Pollutants / Q000097:blood / Q000378:metabolism / Q000633:toxicity; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000037:antagonists & inhibitors* / Q000097:blood / Q000235:genetics / Q000378:metabolism; D007728:Kupffer Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007964:Leukocytosis / Q000209:etiology*; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D018746:Systemic Inflammatory Response Syndrome / Q000139:chemically induced / Q000209:etiology* / Q000503:physiopathology; D013997:Time Factors; D014018:Tissue Distribution; D066007:Toxicokinetics
chemical_list: D004731:Endotoxins; D004785:Environmental Pollutants; D008070:Lipopolysaccharides; D002104:Cadmium; D016179:Granulocyte Colony-Stimulating Factor; C044101:endotoxin, Escherichia coli
keywords: Cadmium; G-CSF; Inflammation; LPS; Mouse; Neutrophil