INFLAMMATORY CELL RECRUITMENT IN ACUTE INJURY

描述：在愈合的伤口内，激活的巨噬细胞分泌大量 可扩散的生长因子、蛋白酶和细胞外基质分子 推进修缮。尽管人们对这些基本功能知道得很多，但 创伤巨噬细胞，对巨噬细胞的作用机制知之甚少 被招募到受伤的地方。私家侦探之前的调查 实验室已证明，单核细胞趋化因子对CC 趋化因子家族包括MCP-1、MIP-1a、MIP-1b和RANTES。 愈合伤口。这一提议的假设是这些CC趋化因子 是巨噬细胞募集和激活的重要介质 受伤。这项提案的长期目标是描述 特异性CC趋化因子在修复过程中的作用。这个 具体目标是：1)确定特定CC的生物学意义 正常伤口修复中的趋化因子，2)评估小鼠伤口愈合情况 在基因上缺乏特定的CC趋化因子，3)检查 CC趋化因子对创面巨噬细胞活化的影响 检查创面内CC趋化因子的功能相互作用。已被占用 总之，这些实验将阐明CC的贡献 趋化因子家族在伤口中对单核细胞的募集和激活。此外， 这些实验将攻击在很大程度上被忽视的CC问题 趋化因子相互作用。这项工作将提供重要的信息 关于正常人巨噬细胞活化和募集机制的研究 伤口修复。这些信息最终可能有助于开发 促进伤口愈合的治疗策略。

DESCRIPTION: Within healing wounds, activated macrophages secrete numerous diffusible growth factors, proteases and extracellular matrix molecules that promote repair. Although much is know about thes essential function of the wound macrophage, little is known about the mechanism by which macrophages are recruited to sites of injury. Previous investigations in the PI's laboratory have demonstrated that monocyte chemoattractants of the CC chemokine family, including MCP-1, MIP-1a, MIP-1b and RANTES are produced in healing wounds. The hypothesis of this proposal is that these CC chemokines are important mediators of macrophage recruitment and activation in sites of injury. The long-term objective of this proposal is to characterize the role of specific CC chemokines in mediating the repair process. The specific aims are 1) to determine the biologic significance of specific CC chemokines in normal wound repair, 2) to assess wound healing in mice that are genetically deficient for specific CC chemokines, 3) to examine the effect of CC chemokines on macrophage activation within wounds, and 4) to examine functional interactions of the CC chemokines within wounds. Taken together, these experiments will elucidate the contribution of the CC chemokine family to monocyte recruitment and activation in wounds. Further, these experiments will attack the largely understudied problem of CC chemokine interaction. This work will provide important information regarding the mechanism of macrophage activation and recruitment in normal wound repair. This information may ultimately assist in the development of therapeutic strategies to facilitate wound healing.