Table 2 Carbon monoxide immunomodulation during transplantation

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)