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Disruption of L-Histidine Decarboxylase Reduces Airway Eosinophilia but not Hyperresponsiveness

2003; American Thoracic Society; Volume: 167; Issue: 5 Linguagem: Inglês

10.1164/rccm.200206-619oc

1535-4970

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,

Polyamine Metabolism and Applications

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.