Eotaxin-1-deficient mice develop airway eosinophilia and airway hyperresponsiveness.
BACKGROUND
The accumulation of eosinophils in the lung is a hallmark of asthma. In addition to cytokines such as IL-5 which are essential, chemokines have been implicated in the recruitment of eosinophils to the airway. In particular, eotaxin has been shown to be a selective and potent eosinophil chemoattractant, important in the pathogenesis of allergic disease. The goal of the present study was to define the role of eotaxin-1 in the development of allergen-induced eosinophilic airway inflammation and airway hyperresponsiveness (AHR) to inhaled methacholine (MCh).


METHODS
Eotaxin-1-deficient mice were sensitized and exposed to a single challenge with allergen. Airway function and airway and tissue as well as peripheral blood and bone marrow eosinophilia were examined 18 and 48 h after the last challenge.


RESULTS
Following allergen sensitization and challenge, eotaxin-1-deficient mice developed levels of AHR to inhaled MCh at 18 and 48 h comparable to controls. Further, levels of bronchoalveolar lavage (BAL) and tissue eosinophilia at the same time points were comparable in the two strains of mice. Tissue eosinophilia, assessed by quantitating major basic protein staining cells, preceded BAL eosinophilia in a similar manner. Bone marrow and peripheral blood eosinophilia were unimpaired in deficient mice.


CONCLUSIONS
The results demonstrate that the major eotaxin, eotaxin-1 is not essential for the development of airway eosinophilia or AHR, implying that other chemokines, alone or in combination, can overcome this deficiency.
Tomkinson
A
A
Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Duez
C
C
Cieslewicz
G
G
Gelfand
E W
EW
D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D001772:Blood Cell Count; D001853:Bone Marrow / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000172:deficiency* / Q000502:physiology*; D005260:Female; D007958:Leukocyte Count; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage / Q000276:immunology; D051379:Mice; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011657:Pulmonary Eosinophilia / Q000276:immunology / Q000503:physiopathology*
D000485:Allergens; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016210:Methacholine Chloride; D010047:Ovalbumin