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

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.