Published ahead of print on December 12, 2002, doi:10.1164/rccm.200206-619OC Am. J. Respir. Crit. Care Med., Volume 167, Number 5, March 2003, 758-763 A more recent version of this article appeared on March 1, 2003
Submitted on August 5, 2002 DISRUPTION OF L-HISTIDINE DECARBOXYLASE REDUCES AIRWAY EOSINOPHILIA BUT NOT HYPERRESPONSIVENESSAKIRA KOARAI1,1 Division of Respiratory and Infectious Diseases, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan, 2 Department of Cellular Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan * To whom correspondence should be addressed. E-mail: ichinose{at}intl.med.tohoku.ac.jp.
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 (HDC) gene knockout mice. Histamine levels of the airways in HDC 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. Further, allergen-induced airway hyperresponsiveness appeared to occur independently of airway eosinophilia in our present model. Key words: asthma, histamine, airway inflammation, airway responsiveness
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