Degranulation patterns of eosinophil granulocytes as determinants of eosinophil driven disease

Background-Degranulation of eosinophils in target tissues is considered a k ey pathogenic event in major chronic eosinophilic diseases. However, becaus e of a lack of appropriate methods, little is known about degranulation of eosinophils in common eosinophilic diseases. Methods-Using transmission electron microscopic (TEM) analysis, a novel app roach has been devised and validated to quantify eosinophil degranulation i n human tissues (assessed in individual cells as percentage granules with s tructural signs of protein release). Biopsy specimens from patients with in flammatory bowel disease, allergic rhinitis, asthma, and nasal polyposis we re evaluated. Results-All conditions displayed a similar degree of local tissue eosinophi lia, with no differences being observed in eosinophil numbers in the airway mucosa of patients with airway diseases and the colonic mucosa of those wi th inflammatory bowel disease (IBD). m contrast, marked differences in the mean (SE) extent of eosinophil degranulation were observed between the pati ent groups; IBD 9.3 (1.4)% altered granules, artificial and natural allerge n challenge induced allergic rhinitis 67.8 (6.8)% and 86.6 (3.0)%, respecti vely, asthma 18.1 (2)%, and nasal polyposis 46.6 (7.6)%. Conclusions-This study provides the first quantitative data which show that different eosinophilic conditions, despite having similar numbers of tissu e eosinophils, may exhibit markedly different degranulation patterns. The p resent assessment of piece-meal degranulation would thus make it possible t o delineate the conditions under which eosinophils are likely to contribute to disease processes. This novel type of analysis may also guide and valid ate antieosinophilic treatment options.