INFLAMMATORY CELL RECRUITMENT IN ACUTE INJURY

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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.