Disruption of L-histidine decarboxylase reduces airway eosinophilia but not hyperresponsiveness

Akira Koarai, Masakazu Ichinose, Satsuki Ishigaki-Suzuki, Shunsuke Yamagata, Hisatoshi Sugiura, Eiko Sakurai, Yoko Makabe-Kobayashi, Atsuo Kuramasu, Takehiko Watanabe, Kunio Shirato, Toshio Hattori, Hiroshi Ohtsu

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)

Abstract

Histamine has a variety of airway actions and is considered to be an important mediator in asthma. This study examined the role of endogenous histamine in allergic airway eosinophil recruitment and hyperresponsiveness using L-histidine decarboxylase gene knockout mice. Histamine levels of the airways in L-histidine decarboxylase knockout mice were largely diminished compared with wild-type mice. Inhalation challenge with ovalbumin (OVA) in OVA-sensitized wild-type mice caused eosinophil accumulation in the lung as well as airway hyperresponsiveness to methacholine 3 days after the challenge. The eosinophil recruitment was significantly reduced in the knockout mice. in the bone marrow, the proliferation of eosinophils was enhanced after OVA challenge in the wild-type mice; however, the proliferation was significantly reduced in the knockout mice. The induction of P-selectin in the lung after OVA challenge was also inhibited in the knockout mice. in contrast, airway hyperresponsiveness was not suppressed in the knockout mice. These results suggest that endogenous histamine is involved in the accumulation of eosinophils into the airways after allergic challenge, possibly acting in the bone marrow and producing P-selectin in the airways. Furthermore, allergen-induced airway hyperresponsiveness appeared to occur independently of airway eosinophilia in our present model.

Original languageEnglish
Pages (from-to)758-763
Number of pages6
JournalAmerican journal of respiratory and critical care medicine
Volume167
Issue number5
DOIs
Publication statusPublished - 2003 Mar 1

Keywords

  • Airway inflammation
  • Airway responsiveness
  • Asthma
  • Histamine

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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