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Effects of Macrophage Supernatants on Mesangial Cell Migration and Hillock Formation

Abstract There is considerable evidence suggesting a role for the macrophage (Mφ) 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 Mφ supernatants (MφSN) 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 MφSN at 24 hr (migration score: MφSN, 24.3 ± 1.3; control, 11.6 ± 1.0, P < 0.001) as well as 48 hr incubation (migration score: MφSN, 34.0 ± 1.4; control, 15.4 ± 1.4, P < 0.001). Enhanced MC migration following prolonged incubation with MφSN was also shown using phase contrast microscopy and scanning electron microscopy. MC hillock formation was enhanced by MφSN in a concentration-related manner as was hillock size. These data demonstrate that MφSN can directly enhance MC migration and hillock formation, processes that may in part account for the observed role for the Mφ in the development of mesangial expansion and GS as well as atherosclerosis.