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

Erjefält, Jonas LU ; Greiff, Lennart LU ; Andersson, Morgan LU ; Matsson, Erik; Petersen, Hannes; Linden, Margareta; Ansari, Tareq; Jeffery, Peter K and Persson, Carl LU (1999) In American Journal of Respiratory and Critical Care Medicine 160(1). p.304-312
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
American Journal of Respiratory and Critical Care Medicine
volume
160
issue
1
pages
304 - 312
publisher
Am Thoracic Soc
external identifiers
  • pmid:10390416
  • scopus:0032772074
ISSN
1535-4970
language
English
LU publication?
yes
id
9b10f9e9-c770-4eeb-88f7-9e82e53f2cb6 (old id 1115985)
alternative location
http://ajrccm.atsjournals.org/cgi/content/full/160/1/304
date added to LUP
2008-07-09 13:43:49
date last changed
2017-11-05 03:49:20
@article{9b10f9e9-c770-4eeb-88f7-9e82e53f2cb6,
  abstract     = {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 &lt; 0. 001) and a higher content of intact granules (p &lt; 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.},
  author       = {Erjefält, Jonas and Greiff, Lennart and Andersson, Morgan and Matsson, Erik and Petersen, Hannes and Linden, Margareta and Ansari, Tareq and Jeffery, Peter K and Persson, Carl},
  issn         = {1535-4970},
  language     = {eng},
  number       = {1},
  pages        = {304--312},
  publisher    = {Am Thoracic Soc},
  series       = {American Journal of Respiratory and Critical Care Medicine},
  title        = {Allergen-induced eosinophil cytolysis is a primary mechanism for granule protein release in human upper airways},
  volume       = {160},
  year         = {1999},
}