Increased Expression of Monocyte Chemoattractant Protein-1 (Mcp-1) in Glomeruli From Rats With Anti Thy 1.1 Glomerulonephritis

The infiltration of monocyte-macrophages in the glomerulus is one of the hallmarks of glomerulonephritis and may play an important pathogenetic role. Monocyte chemoattractant protein-1 (MCP-1) and colony stimulating factor-1 (CSF-1) are monocyte-specific cytokines with chemoattractant and activating activities for monocytes. MCP-1 and CSF-1 can be generated by several cell types including glomerular mesangial cells and can be stimulated by cytokines and immune complexes. To study the expression of CSF-1 and MCP-1 in a model of proliferative glomerulonephritis we used Northern blot analysis and immunohistochemistry. The glomerular lesion was induced in rats by the i.v. injection of a heterologous antibody, directed against the Thy 1.1 antigen which is localized on glomerular mesangial cells. Northern blot analysis revealed comparable amounts of CSF-1 in glomeruli isolated from control, untreated rats, and from rats after 30 min to 3 wks of injection of Thy 1.1. In contrast, control glomeruli contained low mRNA levels for MCP-1, which markedly increased 30 min after the induction of the nephritis, were then reduced at 24 hours and increased again at 5 and 21 days after induction of the disease. These time points following antibody injection are associated with mesangial immune complex formation (30 min), mesangiolysis (24 hours) and proliferative glomerulonephritis (5 and 21 days). By immunohistology the presence of MCP-1 was demonstrated only in glomeruli with a predominant mesangial distribution. The mesangial immunoflourescence for MCP-1 followed a pattern similar to that of the mRNA for MCP-1 after induction of the disease process, i.e. it increased after 30 min, decreased after 24 hrs and was increased again at 3 weeks. Within 30 min of the antibody injection an increased infiltration of monocytemacrophages was observed in the glomeruli, which was maintained up to 3 wks of induction of the glomerulonephritis.