Histamine type 1 receptor deficiency reduces airway inflammation in a murine asthma model.
BACKGROUND
Histamine plays an important role in immediate and late immune responses. The histamine type 1 (H1) receptor is expressed on several immune cell populations, but its role in a murine model of asthma remains unclear. The present study evaluated the role of histamine H1 receptors in airway allergic inflammation by comparing the development of bronchial asthma in histamine H1 receptor gene knockout (H1RKO) and wild-type mice.


METHODS
H1RKO and wild-type mice were sensitized by intraperitoneal injection of ovalbumin (OVA) or saline, and then challenged with aerosolized OVA or saline. Ventilatory timing in response to inhaled methacholine was measured, and samples of blood, bronchoalveolar lavage, and lung tissues were taken 24 h after the last OVA challenge.


RESULTS
OVA-treatedwild-type mice showed significantly increased airway eosinophilic infiltration, and airway response to methacholine compared to OVA-treated H1RKO mice. The serum level of immunoglobulin E and levels of interleukin (IL)-4, IL-5, IL-13, and TGF-beta1 in bronchoalveolar lavage fluid were lower in OVA-treated H1RKO mice than in OVA-treated wild-type mice, but there was no significant difference in interferon-gamma expression. Overall, deletion of histamine H1 receptors reduced allergic responses in a murine model of bronchial asthma.


CONCLUSIONS
Histamine plays an important role via H1 receptors in the development of T helper type 2 responses to enhance airway inflammation.
Miyamoto
Kenichi
K
Second Department of Physiology, Showa University School of Medicine, Tokyo, Japan.
Iwase
Michiko
M
Nyui
Miki
M
Arata
Satoru
S
Sakai
Yasushi
Y
Gabazza
Esteban C
EC
Kimura
Hiroshi
H
Homma
Ikuo
I