Allergen-induced eosinophil cytolysis is a primary mechanism for granule protein release in human upper airways

Cytotoxic eosinophil granule proteins are considered important in the patho genesis of allergic airway diseases such as rhinitis and asthma. To explore the cellular mechanisms behind eosinophil granule release in human allergi c airways, 16 symptom-free patients with seasonal allergic rhinitis were ch allenged daily with allergen during 1 wk. Nasal ravage samples and biopsies , obtained before and 24 h after the last allergen exposure, were processed for immunohistochemical and electron microscopic analysis. The allergen ch allenges produced nasal symptoms, marked tissue eosinophilia, and an increa se in lavage fluid levels of eosinophil cationic protein (ECP). The nasal m ucosa areas with intense extracellular immunoreactivity for ECP were associ ated with abundant free eosinophil granules. Electron microscopy confirmed the free granules and revealed that all mucosal eosinophils were involved i n granule release, either by cytolysis (33%) or piecemeal degranulation (PM D) (67%). Resting or apoptotic eosinophils were not observed. Cytolytic eos inophils had less signs of intracellular granule release (p < 0.001) and a higher content of intact granules (p < 0.001) compared with viable eosinoph ils in the same tissue. This study demonstrates eosinophil cytolysis (ECL) as a distinct mechanism for granule mediator release in human allergic airw ay mucosa. The nature and extent of the ECL and its product (i.e., protein- laden extracellular granules) indicate that allergen-induced cytolysis is a primary and major mechanism for the release of eosinophil proteins in huma n allergic airway inflammation in vivo.