title: Disruption of L-histidine decarboxylase reduces airway eosinophilia but not hyperresponsiveness.
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.
authors.affiliation: Division of Respiratory and Infectious Diseases and Department of Cellular Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Koarai
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ichinose
authors.forename: Satsuki
authors.initials: S
authors.lastname: Ishigaki-Suzuki
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Yamagata
authors.forename: Hisatoshi
authors.initials: H
authors.lastname: Sugiura
authors.forename: Eiko
authors.initials: E
authors.lastname: Sakurai
authors.forename: Yoko
authors.initials: Y
authors.lastname: Makabe-Kobayashi
authors.forename: Atsuo
authors.initials: A
authors.lastname: Kuramasu
authors.forename: Takehiko
authors.initials: T
authors.lastname: Watanabe
authors.forename: Kunio
authors.initials: K
authors.lastname: Shirato
authors.forename: Toshio
authors.initials: T
authors.lastname: Hattori
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohtsu
mesh_terms: D000280:Administration, Inhalation; D000403:Airway Resistance; D000818:Animals; D001249:Asthma / Q000503:physiopathology*; D001854:Bone Marrow Cells / Q000166:cytology; D016535:Bronchial Hyperreactivity; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016085:Bronchoconstrictor Agents; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D004802:Eosinophilia / Q000209:etiology*; D004804:Eosinophils / Q000166:cytology; D006632:Histamine / Q000032:analysis / Q000502:physiology*; D006640:Histidine Decarboxylase / Q000235:genetics*; D015151:Immunoblotting; D015848:Interleukin-5 / Q000032:analysis; D007958:Leukocyte Count; D008168:Lung / Q000737:chemistry; D008297:Male; D016210:Methacholine Chloride; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D010047:Ovalbumin / Q000008:administration & dosage; D011657:Pulmonary Eosinophilia / Q000209:etiology; D019087:Selectins / Q000032:analysis*; D013997:Time Factors
chemical_list: D016085:Bronchoconstrictor Agents; D015848:Interleukin-5; D019087:Selectins; D016210:Methacholine Chloride; D006632:Histamine; D010047:Ovalbumin; D006640:Histidine Decarboxylase