| 1. |
- Erjefält, Jonas, et al.
(författare)
-
Allergen-induced eosinophil cytolysis is a primary mechanism for granule protein release in human upper airways
- 1999
-
Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1535-4970. ; 160:1, s. 304-312
-
Tidskriftsartikel (refereegranskat)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 < 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.
|
|
| 2. |
- Erjefält, Jonas, et al.
(författare)
-
Cytolysis and piecemeal degranulation as distinct modes of activation of airway mucosal eosinophils
- 1998
-
Ingår i: Journal of Allergy and Clinical Immunology. - 1097-6825. ; 102:2, s. 286-294
-
Tidskriftsartikel (refereegranskat)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 < .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.
|
|
