The effect of leukotriene D(4) inhalation on the antigen-induced airway hyperresponsiveness and inflammation in 5-lipoxygenase gene-deficient mice.
BACKGROUND
The role of 5-lipoxygenase (5-LO) products in the asthmatic bronchoconstriction is evident. However, the role of 5-LO products in airway hyperresponsiveness (AHR) and airway inflammation is still under discussion. The aim of the present study is to investigate the role of leukotriene D(4) (LTD(4)) in AHR and allergic airway eosinophilia in mice.


METHODS
The effect of LTD(4) inhalation on antigen-induced AHR and airway eosinophilia was investigated in 5-LO gene-deficient mice.


RESULTS
After three inhalations of LTD(4), airway responsiveness to acetylcholine was not altered in normal or allergic wild-type and 5-LO knockout (KO) mice. In contrast, the number of eosinophils in 5-LO KO allergic mice increased to the level of wild-type allergic mice after the inhalation of LTD(4). These observations were confirmed by a histopathological study of the lungs. No change in the cytokine levels in bronchoalveolar lavage fluid and serum immunoglobulin levels was shown after LTD(4) inhalation.


CONCLUSIONS
These findings suggest that LTD(4) plays a role in eosinophilic airway inflammation but not in AHR in mice.
Kawada
N
N
Department of Pharmacology, Gifu Pharmaceutical University, Gifu, Japan.
Yamada
T
T
Takahashi
Y
Y
Tokuoka
S
S
Masuda
T
T
Tanaka
H
H
Nagai
H
H
D000280:Administration, Inhalation; D000818:Animals; D000941:Antigens / Q000276:immunology*; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics*; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D017998:Leukotriene D4 / Q000008:administration & dosage*; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011657:Pulmonary Eosinophilia / Q000276:immunology / Q000503:physiopathology*
D000941:Antigens; D007074:Immunoglobulin G; D007073:Immunoglobulin E; D017998:Leukotriene D4; D001094:Arachidonate 5-Lipoxygenase