Effects of macrophage supernatants on mesangial cell migration and hillock formation.

There is considerable evidence suggesting a role for the macrophage (M phi) in the development of glomerulosclerosis (GS) and atherosclerosis, lesions which appear to be analogous. Migration of mesangial cells (MC), which are modified smooth muscle cells, may play a role in the pathogenesis of glomerular injury, and smooth muscle migration may play a role in the pathogenesis of atherosclerosis as well. We undertook the present study to determine the effects of M phi supernatants (M phi SN) on MC migration and formation of MC hillocks, which are considered an in vitro model of GS. By means of a migration assay using wounded cultures of confluent, growth-arrested MC, MC migration was found to be significantly enhanced by incubation with M phi SN at 24 hr (migration score: M phi SN, 24.3 +/- 1.3; control, 11.6 +/- 1.0, P < 0.001) as well as 48 hr incubation (migration score: M phi SN, 34.0 +/- 1.4; control, 15.4 +/- 1.4, P < 0.001). Enhanced MC migration following prolonged incubation with M phi SN was also shown using phase contrast microscopy and scanning electron microscopy. MC hillock formation was enhanced by M phi SN in a concentration-related manner as was hillock size. These data demonstrate that M phi SN can directly enhance MC migration and hillock formation, processes that may in part account for the observed role for the M phi in the development of mesangial expansion and GS as well as atherosclerosis.