A pathogenetic role for M1 macrophages in peritoneal dialysis-associated fibrosis.

Peritoneal fibrosis (PF) is a frequent complication of peritoneal dialysis (PD) accompanied by the infiltration of inflammatory cells. Recently, the function of macrophages in an inflammatory microenvironment during PD remains unknown. This study aimed to elucidate the role of distinct macrophage phenotypes in the progression of PF through macrophage depletion in a peritoneal dialysis-induced mouse model. After injection of 200 μl liposomal clodronate (LC) at the start of instillation PD fluids (PDFs), mice were injected with 100 μL LC every 4 days after the first time injection for longer macrophage depletion, while control mice were co-treated with PBS liposomes. For macrophages transfusion,primary macrophages (M0) were stimulated into M1 and M2 macrophages and transfuritoneal fibrosis (PF) is a frequent complication of peritoneal dialysis (PD) accompanied by the infiltration of inflammatory cells. Recently, the function of macrophages in an inflammatory microenvironment during PD remains unknown. This study aimed to elucidate the role of distinct macrophage phenotypes in the progression of PF through macrophage depletion in a peritoneal dialysis-induced mouse model. After injection of 200 μl liposomal clodronate (LC) at the start of instillation PD fluids (PDFs), mice were injected with 100 μL LC every 4 days after the first time injection for longer macrophage depletion, while control mice were co-treated with PBS liposomes. For macrophages transfusion,primary macrophages (M0) were stimulated into M1 and M2 macrophages and transfused into the mice the next day after each LC injection. Mice were sacrificed after 6 weeks of PDFs treatment for the assessment of histological changes, ECM deposition and peritoneal ultrafiltration function. Systemic monocyte/macrophage depletion resulted in less severe structural alterations, including thickening and cubic transformation of mesothelial cells, fibrin deposition, fibrous capsule formation, and interstitial fibrosis. A strong reduction of alpha-smooth muscle actin (α-SMA) and fibronectin expression, as well as an increased E-cadherin expression was also observed, indicating an overall inhibition of peritoneal fibrosis in macrophages depletion mice.M1 macrophage reperfusion showed a significant increase in histological damages, ECM deposition and peritoneal ultrafiltration functional decline compared with those of the M2 and control groups. TLR4 expression was enhanced in M1 macrophage-treated group. These results suggest that M1 macrophages are an important mediator of peritoneal fibrosis.