Matrix-mesangial cell interaction modulates migration of macrophages

Background: Macrophages (M phi s) have been demonstrated to play an importa nt role in immune-mediated renal injury. Accumulation of macrophages in the mesangium has been reported to be a key event in the development of focal glomerulosclerosis, We hypothesized that mesangial cells (MCs) and matrix i nteraction may be a determinant for the migration of M phi s into the mesan gium, Therefore, we studied the effect of the interaction between matrix an d MCs on the migration of M phi s. Methods: Mouse MCs were plated on Petri dishes coated either with buffer, c ollagen type I, III, IV, or Matrigel in media containing 1% fetal calf seru m for 48 hours. Subsequently, supernatants were collected and stored. The e ffect of these supernatants (conditioned media) was evaluated on the migrat ion of M phi s across a filter in a modified Boyden chamber. Results: Conditioned media from MCs grown on Matrigel (MC-Matrigel interact ion products, MC-MGP) enhanced the migration of macrophages across a filter in a modified Boyden chamber when compared with conditioned media from MCs grown on plastic, collagen type I, type III, or type IV (MC-PP, MC-CI, MC- CIII, and MC-CIV), MC-MGP enhanced the migration of M phi s in a dose depen dent manner. Anti-MCP-1 antibodies attenuated (P<0.05) the MC-MGP-induced M phi migration (MC-MGP, 16.8 +/- 2.5 vs MC-MGP + anti-MCP-1 antibody, 6.5 /- 1.2 migrated macrophages/field, n=12), Anti-TGF-beta antibodies did not attenuate MC-MGP-induced M phi migration. MCs grown on Matrigel showed a 5- fold increase of MCP-1 mRNA when compared with cells grown on plastic or co llagen type IV. Conclusions: The present study suggests that matrix components may modulate the migration of M phi s. This effect of MC-matrix interaction on macropha ge migration may be mediated through the generation of MCP-1.