CYTOLYSIS AND PIECEMEAL DEGRANULATION AS DISTINCT MODES OF ACTIVATIONOF AIRWAY MUCOSAL EOSINOPHILS

Background: Cytotoxic eosinophil granule proteins are considered impor tant in the pathogenesis of inflammatory airway diseases, including as thma, rhinitis, and polyposis. However, little is known about the mech anisms involved in the deposition of these tissue-damaging granular pr oducts in vivo. Objective: We sought to determine the occurrence of de granulating eosinophils, those with morphologic evidence of cytolysis with associated clusters of free eosinophil granules (Cfegs), and to i dentify the frequency of apoptotic eosinophils in inflamed upper airwa y tissue. Methods: Eosinophil-rich nasal polyps were processed for tra nsmission electron microscopy and for light microscopic evaluation of whole-mount preparations subjected to deep tissue staining for eosinop hil peroxidase. Results: The mean proportion of eosinophil subtypes we re intact and resting (6.8%), intact but degranulating (83%), cytolyti c or Cfegs (9.9%), and apoptotic (0.0%). All degranulating eosinophils exhibited piecemeal degranulation, The occurrence of Cfegs was confir med in nonsectioned whole-mount preparations. Depending on the appeara nce of their core and matrix, the specific granules were divided into four subtypes, and a degranulation index (altered per total granules) was calculated for each eosinophil. Cytolytic eosinophils had a much l ower degranulation index than intact eosinophils present in the same t issue (P <.001). Conclusions: These data indicate that eosinophil cyto lysis is present in human airway mucosa, that its occurrence is not an artifact of the means of tissue handling, and that cytolysis of eosin ophils may occur without prior extensive degranulation, We suggest tha t eosinophil cytolysis is a major activation mechanism, which occurs a long with, but is distinct from, other types of degranulation.