Disruption of L-histidine decarboxylase reduces airway eosinophilia but not hyperresponsiveness.
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.
Koarai
Akira
A
Division of Respiratory and Infectious Diseases and Department of Cellular Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Ichinose
Masakazu
M
Ishigaki-Suzuki
Satsuki
S
Yamagata
Shunsuke
S
Sugiura
Hisatoshi
H
Sakurai
Eiko
E
Makabe-Kobayashi
Yoko
Y
Kuramasu
Atsuo
A
Watanabe
Takehiko
T
Shirato
Kunio
K
Hattori
Toshio
T
Ohtsu
Hiroshi
H
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
D016085:Bronchoconstrictor Agents; D015848:Interleukin-5; D019087:Selectins; D016210:Methacholine Chloride; D006632:Histamine; D010047:Ovalbumin; D006640:Histidine Decarboxylase