MONOCYTE/MACROPHAGE FUNCTION

and functions as a negative regulator of Ras activity. Loss of neurofibromin, as observed in persons with neurofibromatosis type 1 (NF1), sensitizes cells to growth factor stimulation and aberrant Ras activation. Some NF1 patients develop arterial stenosis in adolescence and early adulthood. We recently showed that loss of a single Nf1 gene copy in myeloid cells is sufficient to induce arterial stenosis after arterial injury and enhance the mobilization of pro-inflammatory Ly6Chi CCR2+ monocytes. Therefore, we tested the hypoth-esis that activation of the MCP-1/CCR2 signaling cascade mediates the re-cruitment of neurofibromin-deficient myeloid cells to induce arterial stenosis. Methods Used: We utilized a carotid artery ligation model to induce neointima formation. The left common carotid artery was ligated proximal to the bifurcation and mice were allowed to recover for 28 days. Control and ligated arteries were analyzed for neointima formation. Nf1+/- mice with genetic deletion of MCP-1 or CCR2 were subjected to arterial injury Separately, chimeric Nf1+/- were generated with specific deletion o