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Cytolysis and piecemeal degranulation as distinct modes of activation of airway mucosal eosinophils

Erjefält, Jonas LU ; Andersson, M; Greiff, Lennart LU ; Korsgren, M; Gizycki, M; Jeffery, P K and Persson, G A (1998) In Journal of Allergy and Clinical Immunology 102(2). p.286-294
Abstract
BACKGROUND: Cytotoxic eosinophil granule proteins are considered important in the pathogenesis of inflammatory airway diseases, including asthma, rhinitis, and polyposis. However, little is known about the mechanisms involved in the deposition of these tissue-damaging granular products in vivo. OBJECTIVE: We sought to determine the occurrence of degranulating eosinophils, those with morphologic evidence of cytolysis with associated clusters of free eosinophil granules (Cfegs), and to identify the frequency of apoptotic eosinophils in inflamed upper airway tissue. METHODS: Eosinophil-rich nasal polyps were processed for transmission electron microscopy and for light microscopic evaluation of whole-mount preparations subjected to deep tissue... (More)
BACKGROUND: Cytotoxic eosinophil granule proteins are considered important in the pathogenesis of inflammatory airway diseases, including asthma, rhinitis, and polyposis. However, little is known about the mechanisms involved in the deposition of these tissue-damaging granular products in vivo. OBJECTIVE: We sought to determine the occurrence of degranulating eosinophils, those with morphologic evidence of cytolysis with associated clusters of free eosinophil granules (Cfegs), and to identify the frequency of apoptotic eosinophils in inflamed upper airway tissue. METHODS: Eosinophil-rich nasal polyps were processed for transmission electron microscopy and for light microscopic evaluation of whole-mount preparations subjected to deep tissue staining for eosinophil peroxidase. RESULTS: The mean proportion of eosinophil subtypes were intact and resting (6.8%), intact but degranulating (83%), cytolytic or Cfegs (9.9%), and apoptotic (0.0%). All degranulating eosinophils exhibited piecemeal degranulation. The occurrence of Cfegs was confirmed in nonsectioned whole-mount preparations. Depending on the appearance 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 lower degranulation index than intact eosinophils present in the same tissue (P < .001). CONCLUSIONS: These data indicate that eosinophil cytolysis is present in human airway mucosa, that its occurrence is not an artifact of the means of tissue handling, and that cytolysis of eosinophils may occur without prior extensive degranulation. We suggest that eosinophil cytolysis is a major activation mechanism, which occurs along with, but is distinct from, other types of degranulation. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Allergy, nasal polyps, eosinophils, cytolysis, apoptosis, degranulation, eosinophil peroxidase, electron microscopy
in
Journal of Allergy and Clinical Immunology
volume
102
issue
2
pages
286 - 294
publisher
Elsevier
external identifiers
  • pmid:9723674
  • scopus:0031783909
ISSN
1097-6825
language
English
LU publication?
yes
id
fc49d80e-6d54-425d-8779-d5cad8f627bc (old id 1113952)
alternative location
http://www.jacionline.org/article/PIIS0091674998700983/fulltext
date added to LUP
2008-07-16 14:17:43
date last changed
2017-11-05 04:36:25
@article{fc49d80e-6d54-425d-8779-d5cad8f627bc,
  abstract     = {BACKGROUND: Cytotoxic eosinophil granule proteins are considered important in the pathogenesis of inflammatory airway diseases, including asthma, rhinitis, and polyposis. However, little is known about the mechanisms involved in the deposition of these tissue-damaging granular products in vivo. OBJECTIVE: We sought to determine the occurrence of degranulating eosinophils, those with morphologic evidence of cytolysis with associated clusters of free eosinophil granules (Cfegs), and to identify the frequency of apoptotic eosinophils in inflamed upper airway tissue. METHODS: Eosinophil-rich nasal polyps were processed for transmission electron microscopy and for light microscopic evaluation of whole-mount preparations subjected to deep tissue staining for eosinophil peroxidase. RESULTS: The mean proportion of eosinophil subtypes were intact and resting (6.8%), intact but degranulating (83%), cytolytic or Cfegs (9.9%), and apoptotic (0.0%). All degranulating eosinophils exhibited piecemeal degranulation. The occurrence of Cfegs was confirmed in nonsectioned whole-mount preparations. Depending on the appearance 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 lower degranulation index than intact eosinophils present in the same tissue (P &lt; .001). CONCLUSIONS: These data indicate that eosinophil cytolysis is present in human airway mucosa, that its occurrence is not an artifact of the means of tissue handling, and that cytolysis of eosinophils may occur without prior extensive degranulation. We suggest that eosinophil cytolysis is a major activation mechanism, which occurs along with, but is distinct from, other types of degranulation.},
  author       = {Erjefält, Jonas and Andersson, M and Greiff, Lennart and Korsgren, M and Gizycki, M and Jeffery, P K and Persson, G A},
  issn         = {1097-6825},
  keyword      = {Allergy,nasal polyps,eosinophils,cytolysis,apoptosis,degranulation,eosinophil peroxidase,electron microscopy},
  language     = {eng},
  number       = {2},
  pages        = {286--294},
  publisher    = {Elsevier},
  series       = {Journal of Allergy and Clinical Immunology},
  title        = {Cytolysis and piecemeal degranulation as distinct modes of activation of airway mucosal eosinophils},
  volume       = {102},
  year         = {1998},
}