INFLAMMATORY CELL RECRUITMENT IN ACUTE INJURY

描述：在愈合的伤口内，活化的巨噬细胞分泌大量的 扩散性生长因子、蛋白酶和细胞外基质分子， 促进修复。 尽管人们对心脏的基本功能了解很多， 创伤巨噬细胞，很少有人知道的机制，巨噬细胞 被招募到受伤的地方 PI的既往研究 实验室已经证明CC单核细胞趋化因子 趋化因子家族，包括MCP-1、MIP-1a、MIP-1b和RANTES，在 愈合伤口 这个提议的假设是这些CC趋化因子 是巨噬细胞募集和激活的重要介质， 损伤 本提案的长期目标是， 特定CC趋化因子在介导修复过程中的作用。 的 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）评估小鼠的伤口愈合， 在遗传上缺乏特定的CC趋化因子，3）检查 CC趋化因子对伤口内巨噬细胞活化的作用，和4） 检查CC趋化因子在伤口内的功能相互作用。 采取 总之，这些实验将阐明CC的贡献 趋化因子家族与伤口中单核细胞的募集和活化。 此外，本发明还 这些实验将解决大部分未被充分研究的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激活和募集的机制， 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.