Cellular Mediator of Thermoregulatory Responses

温度调节反应的细胞介质

• 批准号: 0554514
• 负责人: Rae Silver
• 金额: --
• 依托单位: Columbia University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-15 至 2009-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0554514&HistoricalAwards=false
• 关键词: Cellular; Mediator; Thermoregulatory; Responses

Mast cells are complex immune cells containing many mediators, though they are best known for their role in allergies (produce histamine) and peripheral inflammation (swelling and redness after a bug bite). Surprisingly, mast cells are found in the brain, and the number of brain mast cells increase under specific normal and pathological conditions. Their location in the brain, near blood vessels, suggests that mast cells are poised to regulate behavioral and physiological responses, including body temperature regulation. Pilot work suggests that blocking mast cell activation can alter the elevated temperature response caused by a pathogen entering the body. We have generated mast cell deficient mice to explore the necessity of these cells for a physiologically appropriate immune response. Experiments involve injecting lipopolysaccharide (a piece of a bacteria cell) and measuring the resulting responses (i.e. body temperature, locomotor activity). This injection acts as a stimulus for mounting the immune system, causing a fever in normal mice, just like the reaction to bacteria. Three experimental groups will be studied: normal, mast cell deficient, and age matched adult deficient mice in which the mast cells have been reconstituted. The mast cell deficient mice are predicted to show little to no temperature change following injection of bacterial cell wall, while the response should be restored to normal in the reconstituted animals. Follow-up studies will explore how mast cells contribute to fever. The discovery that mast cells participate in thermoregulation would represent a revolutionizing instance of immune cells impacting physiology and behavior. In addition, the contribution of mast cells in the brain could change the current thinking that the brain is an immune-privileged site and further support the notion that non-neuronal cells in the brain contribute to the control of behavior. This project willprovide unique training opportunities for undergraduate and graduate students in the lab.

肥大细胞是包含许多介质的复杂免疫细胞，尽管它们以其在过敏（产生组胺）和周围炎症（虫子咬合后肿胀和发红）中的作用而闻名。令人惊讶的是，在大脑中发现了肥大细胞，并且在特定的正常和病理条件下，脑肥大细胞的数量增加。它们在血管附近的大脑中的位置表明，肥大细胞有望调节行为和生理反应，包括体温调节。 试点工作表明，阻断肥大细胞激活可以改变由病原体进入人体引起的升高温度反应。我们已经产生了肥大细胞缺乏小鼠，以探索这些细胞的必要性，以进行生理适当的免疫反应。 实验涉及注入脂多糖（细菌细胞）并测量所得反应（即体温，运动活性）。 这种注射是安装免疫系统的刺激，就像对细菌的反应一样，在正常小鼠中引起发烧。将研究三个实验组：正常，肥大细胞不足和年龄相匹配的成年小鼠，其中肥大细胞已重构。预测细菌细胞壁后，缺乏肥大细胞的小鼠几乎没有变化，而在重构动物中应恢复反应为正常。 后续研究将探讨肥大细胞如何促进发烧。 肥大细胞参与体温调节的发现将代表影响生理和行为的免疫细胞的革命实例。 此外，大脑中肥大细胞的贡献可能会改变当前的思想，即大脑是一个免疫特异性部位，并进一步支持以下观点：大脑中的非神经细胞有助于控制行为。 该项目将为实验室的本科和研究生提供独特的培训机会。