Plasma extravasation induced by dietary supplemented histamine in histamine-free mice

Hiroshi Ohtsu, Atsuo Kuramasu, Satoshi Tanaka, Tadashi Terui, Noriyasu Hirasawa, Masahiro Hara, Yoko Makabe-Kobayashi, Noboru Yamada, Kazuhiko Yanai, Eiko Sakurai, Mikiko Okada, Kazuo Ohuchi, Atsushi Ichikawa, Andras Nagy, Takehiko Watanabe

Research output: Contribution to journalArticlepeer-review

65 Citations (Scopus)


Histidine decarboxylase (HDC) synthesizes endogenous histamine from histidine in mammals. To evaluate the role of histamine in skin allergic reaction, we used HDC gene knockout mice lacking histamine. No plasma extravasation reaction was observed in HDC(-/-) mice after passive cutaneous anaphylaxis (PCA) test. Compound 48/80, a mast cell granule depletor, produced plasma extravasation in HDC(+/+) mice but no extravasation in HDC(-/-) mice. Interestingly, orally administered histamine was distributed in the skin in HDC(-/-) mice and in these histamine-supplemented mice the plasma extravasation reaction was observed after the injection of compound 48/80 and the PCA test. Cultured bone marrow-derived mast cells of HDC(-/-) mice took up histamine from the histamine-supplemented medium into the secretory granules. The absorbed histamine was released in response to the same antigen and antibody combination used as in PCA test. In contrast to the immediate-type response, the delayed-type hypersensitive response, observed as a thickening of the ear skin after trinitrochlorobenzene challenge (following sensitization), showed no differences between HDC(+/+) and HDC(-/-) mice. Therefore, among the allergic skin reactions, histamine is revealed to be an important mediator especially for the plasma extravasation in an immediate-type allergy model.

Original languageEnglish
Pages (from-to)1698-1708
Number of pages11
JournalEuropean Journal of Immunology
Issue number6
Publication statusPublished - 2002


  • Edema
  • Hypersensitivity
  • Knockout
  • Mast cell
  • Mouse

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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