Modulation of inflammation and tissue repair by mast cells in skeletal muscle

骨骼肌肥大细胞调节炎症和组织修复

• 批准号: 2287-2008
• 负责人: Côté, Claude
• 金额: $ 2.55万
• 依托单位: Université Laval
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=504172
• 关键词: Modulation; inflammation; tissue; repair; mast

Except for a few dystrophic diseases, injury to muscle-tendon unit is not a life threatening disease, but a very common problem in sports and in the work place. This class of injury accounts for 2,200,000 days of hospital care every year in Canada (Canadian Institute of Information). In USA, statistics released in 2001 at the American College of Sports Medicine meeting reveal that musculoskeletal disorders account for the loss of 21 millions school days and 147 millions work days. It was estimated that all this costs $250 billions a year. Consequently, 30 billions NSAID tablets are consumed every year. It is clearly one of the most neglected class of trauma in society. While preventive care measures have to be put forward, a better understanding of the mechanisms behind muscle tissue injury and repair will lead to a better management of these injuries and to more cost-effective treatments and strategies. Tissue healing is a carefully orchestrated series of cellular events involving inflammatory cells which must first leave the blood stream before they can interact in the injured tissue and lead to repair. In the present proposal, we intend to identify which cells can produce pro- or anti-inflammatory signals that contribute to the persistence or resolution of inflammation and those that can trigger tissue repair. We also want to characterize the time frame of implication for each one of these cells. In this proposal we will focuss more specifically on one type of immune cells, the mast cell. Our working hypothesis is that mast cells play key roles, not only in governing the inflammatory response, but also in modulating its resolution and the tissue repair phase. We will thus 1) Evaluate the importance of mast cell activation in modulating inflammatory cell invasion in muscle damage 2) Determine if mast cells help resolve inflammation through production of anti-inflammatory mediators and 3) Investigate the putative implication of mast cells in the regeneration phase of muscle healing and its mechanism of action. The model used in most cases is the injury in a hindlimb muscle of rat caused by injection of a toxic drug.

除了少数营养不良性疾病外，肌肉肌腱单位损伤并不是危及生命的疾病，而是运动和工作场所中非常常见的问题。在加拿大，此类伤害每年导致 2,200,000 天的住院治疗（加拿大信息研究所）。在美国，2001年美国运动医学会会议上公布的统计数据显示，肌肉骨骼疾病导致了2100万个上学日和1.47亿个工作日的损失。据估计，所有这些每年花费 2500 亿美元。因此，每年消耗 300 亿片 NSAID 药片。它显然是社会上最被忽视的创伤类别之一。虽然必须提出预防性护理措施，但更好地了解肌肉组织损伤和修复背后的机制将有助于更好地管理这些损伤，并制定更具成本效益的治疗和策略。组织愈合是一系列精心策划的涉及炎症细胞的细胞事件，炎症细胞必须首先离开血流，然后才能与受损组织相互作用并导致修复。在本提案中，我们打算确定哪些细胞可以产生有助于炎症持续或消退的促炎或抗炎信号，以及哪些细胞可以触发组织修复。我们还想描述每个单元格的影响时间范围。在本提案中，我们将更具体地关注一种类型的免疫细胞，即肥大细胞。我们的工作假设是，肥大细胞不仅在控制炎症反应方面发挥着关键作用，而且在调节其消退和组织修复阶段方面也发挥着关键作用。因此，我们将1）评估肥大细胞激活在调节肌肉损伤中炎症细胞侵袭中的重要性2）确定肥大细胞是否通过产生抗炎介质帮助解决炎症以及3）研究肥大细胞在肌肉愈合再生阶段的推定意义及其作用机制。大多数情况下使用的模型是注射有毒药物造成的大鼠后肢肌肉损伤。