The importance of leukotrienes in airway inflammation in a mouse model of asthma.
Inhalation of antigen in immunized mice induces an infiltration of eosinophils into the airways and increased bronchial hyperreactivity as are observed in human asthma. We employed a model of late-phase allergic pulmonary inflammation in mice to address the role of leukotrienes (LT) in mediating airway eosinophilia and hyperreactivity to methacholine. Allergen intranasal challenge in OVA-sensitized mice induced LTB4 and LTC4 release into the airspace, widespread mucus occlusion of the airways, leukocytic infiltration of the airway tissue and broncho-alveolar lavage fluid that was predominantly eosinophils, and bronchial hyperreactivity to methacholine. Specific inhibitors of 5-lipoxygenase and 5-lipoxygenase-activating protein (FLAP) blocked airway mucus release and infiltration by eosinophils indicating a key role for leukotrienes in these features of allergic pulmonary inflammation. The role of leukotrienes or eosinophils in mediating airway hyperresponsiveness to aeroallergen could not be established, however, in this murine model.
Henderson
W R
WR
Department of Medicine, University of Washington, Seattle 98195, USA.
Lewis
D B
DB
Albert
R K
RK
Zhang
Y
Y
Lamm
W J
WJ
Chiang
G K
GK
Jones
F
F
Eriksen
P
P
Tien
Y T
YT
Jonas
M
M
Chi
E Y
EY
D058927:5-Lipoxygenase-Activating Proteins; D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D004195:Disease Models, Animal; D005260:Female; D007073:Immunoglobulin E / Q000096:biosynthesis; D007249:Inflammation / Q000209:etiology; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017997:Leukotriene C4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors; D008565:Membrane Proteins / Q000037:antagonists & inhibitors; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009093:Mucus / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D011657:Pulmonary Eosinophilia / Q000209:etiology*; D012129:Respiratory Function Tests; D012137:Respiratory System
D058927:5-Lipoxygenase-Activating Proteins; C548592:ALOX5AP protein, human; D000485:Allergens; C548593:Alox5ap protein, mouse; D016085:Bronchoconstrictor Agents; D002352:Carrier Proteins; D016859:Lipoxygenase Inhibitors; D008565:Membrane Proteins; D016210:Methacholine Chloride; D007975:Leukotriene B4; D017997:Leukotriene C4; D007073:Immunoglobulin E; D010047:Ovalbumin