Abstract
Background
Macrophages (Mφs) have been demonstrated to play an important 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 interaction may be a determinant for the migration of Mφs into the mesangium. Therefore, we studied the effect of the interaction between matrix and MCs on the migration of Mφs.
Methods
Mouse MCs were plated on Petri dishes coated either with buffer, collagen type I, III, IV, or Matrigel in media containing 1% fetal calf serum for 48 hours. Subsequently, supernatants were collected and stored. The effect of these supernatants (conditioned media) was evaluated on the migration of Mφs across a filter in a modified Boyden chamber.
Results
Conditioned media from MCs grown on Matrigel (MC-Matrigel interaction 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 Mφs in a dose dependent manner. Anti-MCP-1 antibodies attenuated (P < 0.05) the MC-MGP-induced Mφ 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-β antibodies did not attenuate MC-MGP-induced Mφ migration. MCs grown on Matrigel showed a 5-fold increase of MCP-1 mRNA when compared with cells grown on plastic or collagen type IV.
Conclusions
The present study suggests that matrix components may modulate the migration of Mφs. This effect of MC-matrix interaction on macrophage migration may be mediated through the generation of MCP-1.
Keywords
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