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[Relationship between tubulointerstitial fibrosis and mononuclear-macrophage]
1Department of Pathology, Peking University School of Basic Medical Sciences, Beijing 100083, China.
Objective:
To study the relationship between monocyte/macrophage (MC/MP) accumulation and tubulointerstitial fibrosis.
Methods:
The renal tubulointerstitial fibrosis model in Wistar rats was established by unilateral renal vein ligature. The rats were fed for 25 days. The kidneys were obtained every 5 days by killing the rats. The morphological changes of tubulointerstitial fibrosis were observed by light microscopy with HE, PAS, PASM and Masson staining. Immunohistochemistry and double immunohistochemistry were used to observe MC/MP accumulation and proliferation. In situ hybridization and immunochemistry were used to observe MCP-1 and M-CSF expression in experimental renal tissue. The MCP-1 protein expression was inspected by Western blot. All the data were analyzed statistically.
Results:
The pathological changes of tubulointerstitial fibrosis were typical. There were many MC/MPs accumulsated in the interstitial space at the early stage and some of them were PCNA positive. At the late stage both accumulation and proliferation of MC/MPs were decreased. The portion of monocyte proliferation was high correlated with the MC/MP accumulation. In situ hybridization showed the positive signals of MCP-1 and M-CSF were mainly located in the cytoplasm of degenerated tubular epithelium and they were strong at the early stage, weak at the late stage. MCP-1 by immunochemistry and Western blot were consistent with in situ hybridization. The MC/MP accumulation was high correlated with the expression of MCP-1 and tubular epithelium degeneration. The portion of monocyte proliferation was high correlated with the expression of M-CSF.
Conclusion:
There was obvious accumulation of MC/MP at the early stage of tubulointerstitial fibrosis. The accumulation came from infiltration and proliferation which were regulated by degenerated tubular epithelial cells producing MCP-1 and M-CSF. MC/MP accumulation was highly correlated with tubular degeneration. MC/MP promoted tubulointerstitial fibrosis and damaged tubular epithelium by secreting a variety of cytokines.