Am. J. Respir. Crit. Care Med., Volume 160, Number 1, July 1999, 304-312

Allergen-induced Eosinophil Cytolysis Is a Primary Mechanism for Granule Protein Release in Human Upper Airways

JONAS S. ERJEFÄLT, LENNART GREIFF, MORGAN ANDERSSON, ERIK MATSSON, HANNES PETERSEN, MARGARETA LINDEN, TAREQ ANSARI, PETER K. JEFFERY, and CARL G. A. PERSSON

Departments of Physiology and Neuroscience, Otolaryngology, and Clinical Pharmacology, University Hospital, Lund, Sweden; Department of Otolaryngology, Reykjavik General Hospital, Reykjavik, Iceland; Preclinical Research, Astra Draco, Lund, Sweden; and Lung Pathology Unit, Asthma and Allergy Research Group, National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom

Cytotoxic eosinophil granule proteins are considered important in the pathogenesis of allergic airway diseases such as rhinitis and asthma. To explore the cellular mechanisms behind eosinophil granule release in human allergic airways, 16 symptom-free patients with seasonal allergic rhinitis were challenged daily with allergen during 1 wk. Nasal lavage samples and biopsies, obtained before and 24 h after the last allergen exposure, were processed for immunohistochemical and electron microscopic analysis. The allergen challenges produced nasal symptoms, marked tissue eosinophilia, and an increase in lavage fluid levels of eosinophil cationic protein (ECP). The nasal mucosa areas with intense extracellular immunoreactivity for ECP were associated with abundant free eosinophil granules. Electron microscopy confirmed the free granules and revealed that all mucosal eosinophils were involved in granule release, either by cytolysis (33%) or piecemeal degranulation (PMD) (67%). Resting or apoptotic eosinophils were not observed. Cytolytic eosinophils had less signs of intracellular granule release (p < 0.001) and a higher content of intact granules (p < 0.001) compared with viable eosinophils in the same tissue. This study demonstrates eosinophil cytolysis (ECL) as a distinct mechanism for granule mediator release in human allergic airway 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 human allergic airway inflammation in vivo.

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