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Macrophage Depletion Improves Chronic Rejection in Rats With Allograft Heart Transplantation.

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BACKGROUND Macrophages may be important in chronic rejection after organ transplantation. This study aimed to investigate the possibility of depleting macrophages for a certain amount of time to alleviate chronic… Click to show full abstract

BACKGROUND Macrophages may be important in chronic rejection after organ transplantation. This study aimed to investigate the possibility of depleting macrophages for a certain amount of time to alleviate chronic rejection in a heart transplant model of Fischer to Lewis rats. METHODS Clodronate liposome was injected abdominally to deplete macrophages for 2 time frames. The expression levels of ectodysplasin 1, arginase 1 (Arg1), chitinase-like lectin (Ym1), interferon gamma, tumor necrosis factor α (TNF-α), smooth muscle α-actin (α-SMA), monocyte chemoattractant protein 1 (MCP-1), and interleukin 10 (IL-10) were detected. RESULTS 1. The expression levels of α-SMA, interferon gamma, TNF-α, and MCP-1 and the transformation of peripheral T cells were lower after macrophage depletion for 2 or 4 weeks. 2. The expression levels of α-SMA, TNF-α, and MCP-1 and the transformation of peripheral T cells were even lower after 4 weeks compared with 2 weeks, except for interferon gamma. 3. A higher level of expression of Arg1 and Ym1 after macrophage depletion for 2 weeks was observed. 4. A higher level of expression of IL-10 after macrophage depletion for 2 weeks, but not 4 weeks, was also observed. CONCLUSIONS Macrophage clearance after heart transplantation alleviated chronic rejection probably via M2 polarization of regenerated macrophages, reduced T-lymphocyte proliferation, and changed the expression levels of interferon gamma, TNF-α, MCP-1, and IL-10.

Keywords: macrophage depletion; chronic rejection; transplantation; expression

Journal Title: Transplantation proceedings
Year Published: 2020

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