Properties of macrophages and lymphocytes appearing in rat renal fibrosis followed by repeated injection of cisplatin

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Properties of macrophages and lymphocytes appearing in renal fibrosis remains to be investigated. F344 rats were injected once a week with cisplatin (2 mg/kg body weight) for 8 weeks and examined at post-final injection weeks 1, 3, 6, 9, and 12. Rats developed progressive renal fibrosis at weeks 1 to 6 as fibrosis-progress phase, and subsequent amelioration at weeks 9 and 12. CD68⁺ M1-macrophages and major histocompatibility complex (MHC) class II⁺ macrophages remarkably increased persistently, whereas CD163⁺ M2-macrophages slightly increased. MHC class II⁺/CD68⁺ and MHC class II⁺/CD163⁺ macrophages were present, indicating that MHC class II⁺ macrophages might have both functions of M1- and M2-macrophages. In the fibrosis-progress phase, interleukin (IL)-6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ for M1-factors, and transforming growth factor (TGF)-β1 and IL-10 for M2-factors tended to increase; tissue injury by M1 and fibrosis by M2 might have occurred simultaneously. Lots of CD4⁺ and CD8⁺ T cells appeared in close relation with MHC class II⁺ macrophages, and mainly CD4⁺ T cells formed aggregations. In the lymphocyte aggregates collected by laser microdissection, expression of IL-17A (for Th17 cells) and forkhead box P3 (FoxP3) (for Treg) significantly increased at weeks 1 and 6, respectively; presumably, Th17 cells might be involved in tissue injury, whereas Treg might be related to fibrosis amelioration. These results suggested that macrophages and T cells may contribute interrelatedly to renal fibrosis.