We hypothesize that chemokines are important mediators of the leukocyte influx and interstitial fibrosis observed in the unilateral ureteral obstruction model (UUO) of hydro-nephrosis. In murine UUO, we have identified the expression of the chemokines RANTES, MIP-2, IP10 and MCP-1. We propose to localize the expression of these chemokines and their receptors in this disease model. Furthermore, we intend to determine if the renin-angiotensin system induces chemokine expression. These studies will be performed using transgenic mice that are null mutants for the angiotensin II receptor, and specific antagonists for the angiotensin II receptors. Since other investigators have determined that MCP-1 can induce the expression of collagen from fibroblasts, we will examine if MCP-1 can induce collagen expression from proximal tubular epithelial cells grown in culture. Finally, our preliminary evidence indicates that dendritic cells infiltrate the obstructed kidney in the rat UUO. We propose to determine if the leukocyte infiltrate in murine UUO is also comprised of dendritic cells.
| Crisman, Jacqueline M; Zhang, Binzhi; Norman, Lourdes P et al. (2004) Deletion of the mouse meprin beta metalloprotease gene diminishes the ability of leukocytes to disseminate through extracellular matrix. J Immunol 172:4510-9 |
