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/W mice. 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/W mice. Histamine inhibited NiCl -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.

Loss of H2R Signaling Disrupts Neutrophil Homeostasis and Promotes Inflammation-Associated Colonic Tumorigenesis in Mice

“…It has been shown that histamine inhibits neutrophil mobility via H2R signaling. 26 We observed that H2R deficiency promoted random migration, as well as fMLP-mediated chemotaxis, in both HDNs and LDNs (Figure 10E). This is in line with the in vivo phenotype, in that more neutrophils infiltrated the areas of intestinal inflammation and colonic tumors.…”

Changes in histidine decarboxylase expression influence extramedullary hematopoiesis in postnatal mice

“…Particularly, Gcsf , whose expression is increased with age in wild‐type mice is decreased in HDC‐KO mice (Figure 7e). This might be directly regulated by HDC expression because high HDC‐expressing myeloid cells are reported to differentiate into granulocytes during inflammation, and these cells simultaneously produce histamine, which enhances HSC dormancy and controls HSC differentiation through the H2 receptor (Kishimoto et al, 2017). Our data thus suggest that expression of these cytokines plays pivotal roles in maintaining a hematopoietic microenvironment in the liver of postnatal mice and that these may be regulated by histamine synthesis.…”

Zinc ions have a potential to attenuate both Ni ion uptake and Ni ion-induced inflammation

“…The protective effects of Zn 2+ at physiological concentrations were also observed in an in vivo model. We had reported that Ni 2+ elution from the Ni wire induced inflammatory events, such as neutrophil infiltration and prostaglandin and histamine production 5 , 6 , and that the initial inflammatory responses induced further elution of Ni 2+ 5 . Using the Ni wire-implanted mouse model, we showed that Ni 2+ -induced inflammation was enhanced in a Zn-deficient state.…”

“…Actually, the prevention of neointima formation by Ni-free stainless stent was demonstrated 4 . We also reported that the implantation of an Ni wire subcutaneously into the back of mice induced the elution of Ni 2+ , the expression of several inflammatory proteins such as cyclooxygenase-2 (COX-2) and neutrophil chemokine macrophage inflammatory protein-2 (MIP-2, CXCL2), and leukocyte infiltration as the initial responses 5 , 6 . Importantly, infiltration and activation of neutrophils enhanced further elution of Ni 2+ 5 .…”