Histamine synthesis is required for granule maturation in murine mast cells

Shunsuke Nakazawa, Mariko Sakanaka, Kazuyuki Furuta, Mayuko Natsuhara, Hirotsugu Takano, Soken Tsuchiya, Yasushi Okuno, Hiroshi Ohtsu, Masahiro Nishibori, Robin L. Thurmond, Noriyasu Hirasawa, Kazuhisa Nakayama, Atsushi Ichikawa, Yukihiko Sugimoto, Satoshi Tanaka

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)


Mast cells are the major sources of histamine, which is released in response to immunological stimulations. The synthesis of histamine is catalyzed by histidine decarboxylase (HDC). Previous studies have shown that Hdc-/- mast cells exhibit aberrant granule morphology with severely decreased granule content. Here, we investigated whether the histamine synthesized in mast cells regulates the granule maturation of murine mast cells. Several genes, including those encoding granule proteases and enzymes involved in heparin biosynthesis, were downregulated in Hdc-/- peritoneal mast cells. Impaired granule maturation was also found in Hdc-/- BM-derived cultured mast cells when they were cocultured with fibroblasts in the presence of c-kit ligand. Exogenous application of histamine and several H4 receptor agonists restored the granule maturation of Hdc-/- cultured mast cells. However, the maturation of granules was largely normal in Hrh4-/- peritoneal mast cells. Depletion of cellular histamine with tetrabenazine, an inhibitor of vesicular monoamine transporter-2, did not affect granule maturation. In vivo experiments with mast cell deficient KitW/KitW-v mice indicated that the expression of the Hdc gene in mast cells is required for granule maturation. These results suggest that histamine promotes granule maturation in mast cells and acts as an proinflammatory mediator.

Original languageEnglish
Pages (from-to)204-214
Number of pages11
JournalEuropean Journal of Immunology
Issue number1
Publication statusPublished - Jan 2014


  • Cell differentiation
  • Histamine
  • Inflammation
  • Mast cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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