Mast cell histamine-mediated transient inflammation following exposure to nickel promotes nickel allergy in mice

Masayuki Kinbara, Kanan Bando, Daisuke Shiraishi, Toshinobu Kuroishi, Yasuhiro Nagai, Hiroshi Ohtsu, Teruko Takano-Yamamoto, Shunji Sugawara, Yasuo Endo

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


We previously reported that allergic responses to nickel (Ni) were minimal in mice deficient in the histamine-forming enzyme histidine decarboxylase (HDC-KO), suggesting an involvement of histamine in allergic responses to Ni. However, it remains unclear how histamine is involved in the process of Ni allergy. Here, we examined the role of histamine in Ni allergy using a murine model previously established by us. Mice were sensitized to Ni by intraperitoneal injection of a NiCl2-lipopolysaccharide (LPS) mixture. Ten days later, allergic inflammation was elicited by challenging ear-pinnas intradermally with NiCl2. Then, ear-swelling was measured. Pyrilamine (histamine H1-receptor antagonist) or cromoglicate (mast cell stabilizer) was intravenously injected 1 h before the sensitization or the challenge. In cell-transfer experiments, spleen cells from Ni-sensitized donor mice were intravenously transferred into non-sensitized recipient mice. In both sensitized and non-sensitized mice, 1 mm or more NiCl2 (injected into ear-pinnas) induced transient non-allergic inflammation (Ni-TI) with accompanying mast cell degranulation. LPS did not affect the magnitude of this Ni-TI. Pyrilamine and cromoglicate reduced either the Ni-TI or the ensuing allergic inflammation when administered before Ni-TI (at either the sensitization or elicitation step), but not if administered when the Ni-TI had subsided. Experiments on HDC-KO and H1-receptor-KO mice, and also cell-transfer experiments using these mice, demonstrated histamine's involvement in both the sensitization and elicitation steps. These results suggest that mast cell histamine-mediated Ni-TI promotes subsequent allergic inflammatory responses to Ni, raising the possibility that control of Ni-TI by drugs may be effective at preventing or reducing Ni allergy.

Original languageEnglish
Pages (from-to)466-471
Number of pages6
JournalExperimental Dermatology
Issue number6
Publication statusPublished - 2016 Jun 1


  • Cromoglicate
  • Dermatitis
  • H1-receptor
  • Histidine decarboxylase
  • Pyrilamine

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology


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