EXPRESSION OF TRANSFORMING GROWTH FACTORS-ALPHA AND BETA(1) MESSENGER-RNA AND PRODUCT BY EOSINOPHILS IN NASAL POLYPS

Nasal polyps are thought to develop as a manifestation of a chronic in flammatory process involving the upper airways. The eosinophil charact eristically represents a prominent component of the inflammatory cell infiltrate of these lesions. However, the major clinical problem assoc iated with nasal polyps, nasal obstruction, reflects the proliferation of die stromal and epithelial elements, which constitute the bulk of these lesions. We recently reported that blood eosinophils of patients with hypereosinophilia can produce the cytokines transforming growth factors-alpha (TGF-alpha) and beta(1) (TGF-beta(1)). These cytokines h ave many biologic activities, which include the regulation of epitheli al proliferation, the promotion of extracellular matrix formation, and the induction of angiogenesis. We therefore used in situ hybridizatio n to determine whether the eosinophils that infiltrate nasal polyps ex press TGF-alpha and/or TGF-beta(1) messenger RNA and used immunohistoc hemistry to determine whether these eosinophils also express TGF-alpha and TGF-beta(1) proteins. We found that eosinophils represented a maj or source of both transforming growth factors in each case of nasal po lyposis examined and that in most cases the majority of all eosinophil s expressed both TGF-alpha and TGF-beta(1). These results suggest that production of TGF-alpha and TGF-beta(1) by the infiltrating eosinophi ls may contribute to some of the pathologic changes observed in nasal polyposis, such as thickening of the epithelial basement membrane, str omal fibrosis, angiogenesis, and epithelial and glandular hyperplasia.