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

被引:99
作者
Erjefält, JS
Greiff, L
Andersson, M
Matsson, E
Petersen, H
Linden, M
Ansari, T
Jeffery, PK
Persson, CGA
机构
[1] Univ Lund Hosp, Dept Physiol & Neurosci, S-22185 Lund, Sweden
[2] Univ Lund Hosp, Dept Otolaryngol, S-22185 Lund, Sweden
[3] Univ Lund Hosp, Dept Clin Pharmacol, S-22185 Lund, Sweden
[4] Reykjavik Gen Hosp, Dept Otolaryngol, Reykjavik, Iceland
[5] Astro Draco AB, Preclin Res, Lund, Sweden
[6] Natl Heart & Lung Inst, Imperial Coll Sch Med, Asthma & Allergy Res Grp, Lung Pathol Unit, London, England
关键词
D O I
10.1164/ajrccm.160.1.9809048
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
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 ravage 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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页码:304 / 312
页数:9
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