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Neutrophil tissue delivery, early immune protection and quality of life in neutropenia.

机译:中性粒细胞减少症的中性粒细胞递送,早期免疫保护和生活质量。

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摘要

The role of neutrophils in maintaining oral health has been well documented and is best understood when examining the poor oral health-related quality of life of children with neutropenia. Under normal conditions, the bacterial presence in the mouth is kept under control by a constant influx of neutrophils from surrounding periodontal tissues. This chemotactic recruitment of neutrophils to the oral cavity inspired us to develop and validate a non-invasive oral rinse assay to study the delivery of neutrophils to the mouth following chemotherapy and bone marrow transplantation (BMT), and to compare this information to circulating neutrophil levels, oral mucositis scores and infection-related fever episodes following blood neutrophil recovery. Using this oral rinse, we showed that oral neutrophils reappeared and returned to a stable level earlier in the mouth than in the blood following BMT, thus enabling us to successfully predict engraftment much sooner than it was evident in their blood counts as per the conventional definition of engraftment. Furthermore, the timing of neutrophil tissue delivery in the mouth was a good indicator of neutrophil functionality and infection susceptibility in the post-BMT setting. Consequently, we developed a mouse BMT model which uses enhanced green fluorescent protein-expressing donor neutrophils. Besides recapitulating the results from our human study, this mouse BMT model allowed us to better understand neutrophil recovery kinetics following transplantation and how they relate to the restoration of cellular immune function post-BMT. Using the model, we have demonstrated that protection against bacterial infection is conferred at the time of neutrophil tissue delivery which always occurs before neutrophils are detected in the blood. These findings reaffirmed the clinical utility of the oral rinse assay to predict engraftment and susceptibility to infection following transplantation. Moreover, the mouse BMT model served as an in vivo cell migration model to study the effectiveness of specific drug therapies on neutrophil recovery and functionality. This animal model has the potential to help us better understand the molecular mechanisms of neutrophil mobilization, and will allow us to begin to identify the biological determinants that influence the rate of neutrophil tissue penetration, their levels and survival in the tissues.
机译:嗜中性粒细胞在维持口腔健康中的作用已得到充分证明,当检查嗜中性白血球缺乏症儿童与口腔健康相关的不良生活质量时,最好能了解中性粒细胞的作用。在正常情况下,口腔中细菌的存在是由周围牙周组织不断流入的中性粒细胞控制的。嗜中性粒细胞向口腔的趋化性吸收激发了我们开发和验证一种非侵入性口腔冲洗法的研究方法,以研究中性粒细胞在化疗和骨髓移植(BMT)后向口腔的递送,并将该信息与循环中性粒细胞水平进行比较血液中性粒细胞恢复后,口腔粘膜炎评分和感染相关的发烧发作。使用这种口腔冲洗液,我们发现口腔中性粒细胞比BMT后在口腔中更早地出现并恢复到口腔中的稳定水平,因此使我们能够比传统定义中的血球计数更早地成功预测移入植入。此外,中性粒细胞在口腔中的递送时间是BMT后环境中中性粒细胞功能和感染敏感性的良好指标。因此,我们开发了一种小鼠BMT模型,该模型使用增强的表达绿色荧光蛋白的供体中性粒细胞。除了概括人类研究的结果外,这种小鼠BMT模型还使我们能够更好地了解移植后中性粒细胞的恢复动力学以及它们与BMT后细胞免疫功能恢复的关系。使用该模型,我们证明了在中性粒细胞组织输送时(通常在血液中检测到中性粒细胞之前)就可以防止细菌感染。这些发现重申了口服漂洗测定法在预测移植后的植入和感染易感性方面的临床实用性。此外,小鼠BMT模型用作体内细胞迁移模型,以研究特定药物疗法对嗜中性白细胞恢复和功能性的有效性。这种动物模型有可能帮助我们更好地了解嗜中性白细胞动员的分子机制,并使我们能够开始确定影响嗜中性白细胞组织渗透速率,其水平和在组织中存活的生物学决定因素。

著录项

  • 作者

    Cheretakis, Chrisovalantou.;

  • 作者单位

    University of Toronto (Canada).;

  • 授予单位 University of Toronto (Canada).;
  • 学科 Health Sciences Dentistry.;Health Sciences Immunology.
  • 学位 Ph.D.
  • 年度 2008
  • 页码 126 p.
  • 总页数 126
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 口腔科学;预防医学、卫生学;
  • 关键词

  • 入库时间 2022-08-17 11:38:35

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