title: Induced histamine regulates Ni elution from an implanted Ni wire in mice by downregulating neutrophil migration.
abstract: Histamine regulates various inflammatory reactions. We have reported that the expression of histidine decarboxylase (HDC) was induced by subcutaneous implantation of nickel (Ni) wire. However, the source and functions of histamine in Ni elution and Ni wire-induced inflammation have not been completely studied. We aimed to elucidate the effects of de novo synthesized histamine on leucocyte infiltration and Ni elution. Implantation of Ni wire induced an increase in the Ni ion content of the surrounding tissues and serum and in the mRNA levels of HDC, a histamine-producing enzyme, macrophage inflammatory protein-2 (MIP-2), a chemoattractant for neutrophils, and monocyte chemoattractant protein-1 (MCP-1), a chemoattractant for monocytes. The Ni wire induced HDC expression even in mast cell-deficient WBB6F1-W/WVmice. In HDC knockout (HDC KO) mice, the Ni wire-induced increase in MIP-2 mRNA expression was significantly higher than that in wild-type mice but not MCP-1. MIP-2 expression was enhanced in histamine H2 receptor knockout (H2R KO) mice but not in WBB6F1-W/WVmice. Histamine inhibited NiCl2-induced MIP-2 mRNA expression in mouse bone marrow-derived macrophages (BMDMs) obtained from wild-type mice; this inhibition was not observed in BMDMs from H2R KO mice. Ni elution increased in HDC KO mice, in which leucocyte infiltration also increased, and was suppressed in mice treated with neutrophil-specific antibody. These results suggest that the Ni wire induced HDC expression in non-mast cells and that, in the chronic phase of inflammation, endogenous histamine reduced Ni elution, probably through regulation of MIP-2 expression and neutrophil migration.
authors.affiliation: Laboratory of Pharmacotherapy of Life-style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Yu
authors.identifier: 0000-0002-8876-0500
authors.initials: Y
authors.lastname: Kishimoto
authors.affiliation: Laboratory of Pharmacotherapy of Life-style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Sanki
authors.initials: S
authors.lastname: Asakawa
authors.affiliation: Laboratory of Pharmacotherapy of Life-style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Taiki
authors.initials: T
authors.lastname: Sato
authors.affiliation: Laboratory of Pharmacotherapy of Life-style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Takano
authors.affiliation: Laboratory of Pharmacotherapy of Life-style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Nakajyo
authors.affiliation: Laboratory of Pharmacotherapy of Life-style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Natsumi
authors.initials: N
authors.lastname: Mizuno
authors.affiliation: Laboratory of Pharmacotherapy of Life-style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Segawa
authors.affiliation: Department of Pharmacology, Graduate School of Medicine, Tohoku University, Sendai, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Yoshikawa
authors.affiliation: Department of Pharmacology, Graduate School of Medicine, Tohoku University, Sendai, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hiratsuka
authors.affiliation: Department of Pharmacology, Graduate School of Medicine, Tohoku University, Sendai, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yanai
authors.affiliation: Department of Quantum Science and Energy Engineering, Graduate School of Engineering, Tohoku University, Sendai, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohtsu
authors.affiliation: Laboratory of Pharmacotherapy of Life-style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Hirasawa
mesh_terms: D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D054426:Chemokine CXCL2 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D015870:Gene Expression / Q000187:drug effects; D006632:Histamine / Q000378:metabolism* / Q000494:pharmacology; D006640:Histidine Decarboxylase / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000502:physiology*; D009532:Nickel / Q000009:adverse effects / Q000378:metabolism* / Q000494:pharmacology; D019736:Prostheses and Implants; D012333:RNA, Messenger / Q000378:metabolism*; D011970:Receptors, Histamine H2 / Q000235:genetics
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D012333:RNA, Messenger; D011970:Receptors, Histamine H2; C022838:nickel chloride; D009532:Nickel; D006632:Histamine; D006640:Histidine Decarboxylase
keywords: H2 receptor; histidine decarboxylase; leukocyte; macrophage inflammatory protein-2; metal implant