Autocrine/paracrine control of vascular smooth muscle cell growth by macrophage colony-stimulating factor.

In several vascular diseases an abnormal of vascular smooth muscle cell (VSMC) proliferation is associated with the presence of macrophages. We therefore examined whether macrophage colony-stimulating factor (M-CSF) might play a role in the control of VSMC growth. VSMCs were isolated from rat aorta and maintained in culture. The influence of M-CSF on DNA synthesis and proto-oncogene expression was assessed by 3H-thymidine incorporation measurement and Northern analysis, respectively. Macrophage colony-stimulating activity (M-CSA) was ascertained by a bioassay. Addition to quiescent VSMCs of various dilutions of L929 serum-free condition medium (S-FCM), as a source of M-CSF, concentration-dependently induced DNA synthesis; this effect could be blunted by the concomitant addition of a specific anti M-CSF antibody. SFCM from L929 also induced and/or modulated the expression of c-fos, c-myc and jun B. Recombinant human M-CSF weakly induced DNA synthesis when added alone, but synergistically enhanced that induced by thrombin, PDGF and bFGF. M-CSA was clearly detected in VSMC-derived S-FCM. The presence of c-fms mRNA and fms oncoprotein, as revealed by Northern blot analysis and immunocytochemistry, respectively, indicated that VSMCs expressed M-CSF receptors. These results support the hypothesis of a paracrine/autocrine mechanism whereby M-CSF could affect the growth of cultured rat VSMCs.