Degranulation patterns of eosinophil granulocytes as determinants of eosinophil driven disease

Abstract

Background-Degranulation of eosinophils in target tissues is considered a key pathogenic event in major chronic eosinophilic diseases. However, because 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 approach has been devised and validated to quantify eosinophil degranulation in human tissues (assessed in individual cells as percentage granules with structural signs of protein release). Biopsy specimens from patients with inflammatory bowel disease, allergic rhinitis, asthma, and nasal polyposis were evaluated. Results-All conditions displayed a similar degree of local tissue eosinophilia, with no diVerences being observed in eosinophil numbers in the airway mucosa of patients with airway diseases and the colonic mucosa of those with inflammatory bowel disease (IBD). In contrast, marked diVerences in the mean (SE) extent of eosinophil degranulation were observed between the patient groups; IBD 9.3 (1.4)% altered granules, artificial and natural allergen challenge induced allergic rhinitis 67.8 (6.8)% and 86.6 (3.0)%, respectively, asthma 18.1 (2)%, and nasal polyposis 46.6 (7.6)%. Conclusions-This study provides the first quantitative data which show that diVerent eosinophilic conditions, despite having similar numbers of tissue eosinophils, may exhibit markedly diVerent degranulation patterns. The present assessment of piecemeal degranulation would thus make it possible to delineate the conditions under which eosinophils are likely to contribute to disease processes. This novel type of analysis may also guide and validate antieosinophilic treatment options. (Thorax 2001;56:341-344)

The rise of the phoenix: the expanding role of the eosinophil in health and disease

“…CD8 + T-cell depletion also prevented the development of virus-induced M2R dysfunction but only in the group that received prior sensitization. The failure to stain eosinophils in the airway of these virusinfected animals could be related to eosinophil degranulation by cytolysis (46,47). Virus-induced eosinophil cytolysis would disperse the granules and decrease the number of whole cells, making the staining of eosinophils more difficult by conventional means.…”

Mechanisms of eosinophil secretion: large vesiculotubular carriers mediate transport and release of granule-derived cytokines and other proteins

“…These gross alterations within secretory granules, indicative of progressive release of their products, are described in a diversity of cell types [7,39,40,54]. In human eosinophils, it is recognized that the number of emptying granules increases in activated cells, in vivo and in vitro, in different conditions [33][34][35][36]43]. Inflammatory stimuli, such as chemokines (eotaxin and RANTES) or platelet-activating factor, trigger PMD, and pretreatment with BFA, a potential inhibitor of vesicular transport [55], inhibits agonist-induced, granule emptying [43].…”

“…PMD is a general secretion process implicated in the release of products from activated eosinophils in a range of human diseases including allergic inflammation [33][34][35][36][37]. PMD has also been identified extensively in other secretory cells [38][39][40].…”

Eosinophil degranulation status in allergic rhinitis: observations before and during seasonal allergen exposure

“…Preliminary results already suggest that eosinophils, occurring in the target tissue during active seasonal allergic rhinitis, may exhibit more pronounced degranulation than in many other common diseases characterised by tissue eosinophilia, e.g. inflammatory bowel disease and asthma [8,9]. However, as yet, little is known about the dynamics of eosinophil degranulation in allergic rhinitis, especially when the disease progresses from a nonsymptomatic baseline situation into an active symptomatic condition.…”

“…It is, therefore, of interest that the occurrence of degranulated eosinophils may vary greatly between different diseases [8]. Thus, in the search for pathogenic roles of the eosinophil, it may be helpful to focus particularly on conditions where the tissue eosinophils are highly degranulated.…”