Temporal role of chemokines in a murine model of cockroach allergen-induced airway hyperreactivity and eosinophilia.
The increase in inner-city asthma among children appears to be due to allergic responses to several allergens. Recent studies have demonstrated that Ags derived from cockroaches are especially prominent in these settings and a significant health concern for the induction of asthma in children. In the present study, we have outlined the development of a murine model of cockroach allergen-induced airway disease and assessed specific mechanisms of the response, which resembles atopic human asthma. The allergic responses in this model include allergen-specific airway eosinophilia and significantly altered airway physiology, which directly correlates with inflammation. We have further utilized this allergen to establish primary and secondary rechallenge stages of late phase hyperreactivity exacerbation. This latter stage is characterized by greater changes in airway physiology than the primary stage, and it is likely due to the preexisting peribronchial inflammation present at the time of the second allergen rechallenge. We have identified specific roles for CC chemokines during these stages, with MIP-1alpha being an important eosinophil attractant during the primary stage and eotaxin during the secondary rechallenge stage. The development of these models allows the evaluation of mediators involved in both stages of cockroach allergen challenge, as well as the testing of specific therapeutic modalities.
Campbell
E M
EM
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109, USA.
Kunkel
S L
SL
Strieter
R M
RM
Lukacs
N W
NW
D000485:Allergens / Q000633:toxicity*; D000818:Animals; D001249:Asthma / Q000209:etiology / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000209:etiology / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D054413:Chemokine CCL11; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC; D002648:Child; D003058:Cockroaches / Q000276:immunology*; D016207:Cytokines / Q000502:physiology*; D004195:Disease Models, Animal; D047209:Eosinophil Peroxidase; D005260:Female; D006801:Humans; D007249:Inflammation; D019402:Macrophage Inflammatory Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010544:Peroxidases / Q000032:analysis; D011657:Pulmonary Eosinophilia / Q000209:etiology / Q000503:physiopathology*
D000485:Allergens; C515456:CCL11 protein, human; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC; D016207:Cytokines; D019402:Macrophage Inflammatory Proteins; D047209:Eosinophil Peroxidase; D010544:Peroxidases