Eosinophil activation of fibroblasts from chronic allergen-induced disease utilizes stem cell factor for phenotypic changes.
In the present studies the role of stem cell factor (SCF) in mediating eosinophil and fibroblast activation during their interaction was investigated. SCF was significantly higher in fibroblasts grown from lungs of chronic allergen-challenged mice compared to fibroblasts grown from normal mice. When eosinophils were layered onto fibroblasts from allergic mice, a significant increase in SCF was detected compared to fibroblasts from nonallergic mice. The interaction of fibroblasts with eosinophils also increased the production of asthma-associated chemokines, CCL5 and CCL6, was dependent on cell-to-cell interaction, and was observed only with fibroblasts derived from lungs of chronic allergen-challenged mice and not from those derived from unchallenged normal mice. Chemokine production was significantly decreased when anti-SCF antibodies were added during eosinophil-fibroblast interaction. The interaction of fibroblasts from chronic allergen-challenged mice with eosinophils also increased alpha-smooth muscle cell actin and procollagen I expression as well as induced transforming growth factor-beta. The changes in myofibroblast activation were dependent on SCF-mediated pathways because anti-SCF antibody treatment reduced the expression of all three of these latter fibrosis-associated markers. Thus, our data suggest that SCF mediates an important activation pathway for fibroblasts during chronic allergic responses on interaction with recruited eosinophils and suggest a potential mechanism of airway remodeling during chronic disease.
D000485:Allergens / Q000378:metabolism*; D000818:Animals; D000941:Antigens / Q000737:chemistry; D018946:Chemokine CCL5 / Q000378:metabolism; D019742:Chemokines, CC / Q000378:metabolism; D018920:Coculture Techniques; D004804:Eosinophils / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D010641:Phenotype; D019089:Stem Cell Factor / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism
D000485:Allergens; D000941:Antigens; C503460:Ccl5 protein, mouse; D018946:Chemokine CCL5; D019742:Chemokines, CC; D019089:Stem Cell Factor; D016212:Transforming Growth Factor beta; C070959:Ccl6 protein, mouse