Erjefält J S, Andersson M, Greiff L, Korsgren M, Gizycki M, Jeffery P K, Persson G A
Department of Physiology and Neuroscience, University Hospital, Lund, Sweden.
J Allergy Clin Immunol. 1998 Aug;102(2):286-94. doi: 10.1016/s0091-6749(98)70098-3.
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.
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.
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.
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).
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.
细胞毒性嗜酸性粒细胞颗粒蛋白在包括哮喘、鼻炎和息肉病在内的炎症性气道疾病的发病机制中被认为很重要。然而，对于这些组织损伤性颗粒产物在体内沉积所涉及的机制知之甚少。
我们试图确定脱颗粒嗜酸性粒细胞的存在情况，即那些具有细胞溶解形态学证据及相关游离嗜酸性粒细胞颗粒簇（Cfegs）的嗜酸性粒细胞，并确定炎症性上呼吸道组织中凋亡嗜酸性粒细胞的频率。
对富含嗜酸性粒细胞的鼻息肉进行处理，用于透射电子显微镜检查以及对经嗜酸性粒细胞过氧化物酶深度组织染色的整装标本进行光学显微镜评估。
嗜酸性粒细胞亚型的平均比例为完整且静止的（6.8%）、完整但正在脱颗粒的（83%）、细胞溶解或有Cfegs的（9.9%）以及凋亡的（0.0%）。所有脱颗粒嗜酸性粒细胞均表现为逐片脱颗粒。在未切片的整装标本中证实了Cfegs的存在。根据其核心和基质的外观，将特异性颗粒分为四种亚型，并为每个嗜酸性粒细胞计算脱颗粒指数（改变的颗粒数除以总颗粒数）。细胞溶解的嗜酸性粒细胞的脱颗粒指数远低于同一组织中存在的完整嗜酸性粒细胞（P <.001）。
这些数据表明，嗜酸性粒细胞细胞溶解存在于人类气道黏膜中，其出现并非组织处理方式造成的假象，并且嗜酸性粒细胞的细胞溶解可能在没有先前广泛脱颗粒的情况下发生。我们认为嗜酸性粒细胞细胞溶解是一种主要的激活机制，它与其他类型的脱颗粒同时发生，但又有所不同。
