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.
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Acknowledgments
This work was supported by a Grant-in-Aid for Scientific Research (C) (No. 15590519) from the Ministry of Education, Science, and Culture of Japan. This publication was subsidized by JKA through its promotion funds from KEIRIN RACE. We thank Prof. Fujio Kayama of Jichi Medical University for financial assistance.
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Horiguchi, H., Oguma, E. Acute exposure to cadmium induces prolonged neutrophilia along with delayed induction of granulocyte colony-stimulating factor in the livers of mice. Arch Toxicol 90, 3005–3015 (2016). https://doi.org/10.1007/s00204-016-1661-7
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DOI: https://doi.org/10.1007/s00204-016-1661-7