Involvement of MCP-1 and M-CSF in glomerular foam cell formation in ExHC rats

Background An increase in glomerular macrophages (MO) is considered a poten tial effector mechanism by which hypercholesterolemia exacerbates glomerula r injury. To investigate the mechanism underlying recruitment of MO into gl omeruli, the expression of glomerular monocyte chemoattractant protein-1 (M CP-1) and macrophage colony stimulating factor (M-CSF) mRNA were examined u sing a lipid-induced glomerular injury rat model. Methods. Eight-week-old male ExHC rats, a strain susceptible to hyperlipide mia, were divided into the following 4 groups: a control group (C), a high cholesterol diet group (HH), a high cholesterol diet/standard diet group (H N), which were fed a high cholesterol diet for the first 4 weeks and a stan dard diet for the following 4 weeks, and a probucol-treatment group (PT). B oth MCP-1 and M-CSF mRNA expression in glomeruli were analyzed using the RT -PCR method. An additional experimental group (M) fed a high cholesterol di et was administered M-CSF daily for 4 weeks. Results. Thr expression of MCP-1 mRNA in glomeruli increased accompanied by an increased total serum cholesterol level in HH and HN. However, M-CSF mR NA expression was significantly suppressed at 1 or 2 weeks and gradually in creased to almost basal levels. In the PT group, MCP-1 mRNA expression was suppressed. The early suppression of M-CSF mRNA expression was inhibited in PT. Renal histology showed a significant increase in foam cells in glomeru li in HH and HN rats at 4 weeks. HH rats showed increased and expanded foam cells at 8 weeks. In HN rats, however, foam cells decreased significantly after the transfer to a standard diet from a high cholesterol diet. The MCP -1 mRNA expression was suppressed after the transfer. In the PT group, foam cell formation was also suppressed. Foam cells were identified as MO. M-CS F-treatment significantly suppressed foam cell formation in glomeruli when compared with the untreated group levels. Conclusion. These findings suggest that hypercholesterolemia stimulated the expression of MCP-1 in glomeruli and attracted the MO into glomeruli, They also suggest that the reduction of hypercholesterolemia after the change i n diet or treatment with probucol suppressed glomerular injury by suppressi ng the glomerular MCP-1 expression. M-CSF may suppress the recruitment of M O into glomeruli and foam cell formation at an early stage of hypercholoste rolemia-induced glomerular injury.