Macrophages and graft vasculature. During acute rejection, macrophages induce microvascular EC injury through the production of ROS, RNS, TNF-α and possibly LTB4. On the other hand, macrophages can also promote microvascular repair through the production of angiogenic factors, such as VEGF, FGF-2, SDF-1 and PLGF. During chronic rejection, macrophages promote SMLC proliferation by producing IFN-γ, PDGF, TNF-α, IL-1, TGF-β and possibly LTB4. Abbreviations: IFN, interferon; ROS, reactive oxygen species; RNS, reactive nitrogen species; TNF, tumor necrosis factor; PDGF, platelet-derived growth factor; IL, interleukin; TGF, transforming growth factor; LTB4, leukotriene B4; SMLCs, smooth muscle-like cells, VEGF, vascular endothelial growth factor; FGF, fibroblast growth factor; SDF, stromal cell-derived factor; PLGF, placental growth factor.