DIRECT DEMONSTRATION OF DELAYED EOSINOPHIL APOPTOSIS AS A MECHANISM CAUSING TISSUE EOSINOPHILIA

Nasal polyps, which often occur in association with allergic rhinitis and asthma, are characterized by a marked infiltration of eosinophils. Using a method for detecting eosinophils with DNA strand breaks, we f ound direct evidence for inhibition of eosinophil apoptosis in this mo del of tissue eosinophilia. By using Southern blot analysis linked to reverse transcription-PCR, we detected a mRNA signal specific for IL-5 in all nasal polyps. The identification of IL-5 as a major eosinophil survival factor was confirmed by ELISA measurements using tissue homo genates. Moreover, immunohistochemical analysis of the nasal polyp tis sues demonstrated that IL-5 was localized in lymphocytes, mast cells, and eosinophils. Treatment of the eosinophil-infiltrated tissue with n eutralizing anti-IL-5 mAb induced eosinophil apoptosis and decreased t issue eosinophilia. Therefore, IL-5 may represent an important cytokin e responsible for the delay of the death process in eosinophils in nas al polyps. In addition, a previously suggested IL-4-dependent specific recruitment of eosinophils into the inflammed tissue could be exclude d by our studies. Taken together, these findings suggest a novel mecha nism by which eosinophils specifically accumulate in pathologic human tissues.