From: The immunomodulatory role of carbon monoxide during transplantation
CO TARGET | CONSEQUENCES |
---|---|
DONOR | ↓Toll-like receptor (TLR)4 |
↓endothelial cell proliferation | |
↓lymphocytic infiltration | |
↓inflammatory cytokines production (IFN-g) | |
↓apoptosis | |
↓Reactive oxygen species (ROS) | |
↓NFκB (IκB degradation) | |
↓E-selectin/ ICAM-1 | |
GRAFT | ↑Hypoxia inducible factor (HIF)-1a |
↑Vascular endothelial growth factor (VEGF) | |
↓apoptosis (↑Bcl-2, ↓Bax, ↓caspase 3) | |
↓inflammatory cytokines production (TNF, IL-6) | |
↓prostaglandin (COX2) | |
↓ICAM-1 | |
↓NFκB | |
RECIPIENT | ↓Ischemia and reperfusion injury |
↓fibrosis | |
↓anti-donor IgG antibodies | |
↓chemokine receptors (CCR1, CXCR3, CXCR5) | |
↓chemokines (IL-8, MIP-1a) | |
↓ICAM-1 | |
↓IL-2 (↓T cell proliferation) | |
↓leukocyte infiltration (CD3+, CD4+, CD8+ T cells and macrophages) | |
↓macrophage activation (↓MHC class II) | |
↓neutrophil activation (↓MPO) | |
↓apoptosis (↓CD95/FasL) | |
↓inflammatory cytokines production (IL-1β, TNF) | |
↓iNOS | |
↓prostaglandin (COX2) | |
↓platelet aggregation | |
↑cell cycle inhibition (↑p21clip1) | |
↑Treg (Foxp3+ T cells) |