Table 1.
Alarmin | Receptor | Impact | References |
---|---|---|---|
Nuclear Proteins | |||
High-mobility group box 1 (HMGB1) |
TLR2, TLR4, RAGE |
Promotes Alloreactive T cell responses, GHVD, and Tx rejection Pre-conditioning protects against I/R injury |
(34) (40) (39) (35) (36) (37) (38) (46) |
IL-1α | IL-1R | (9) | |
IL-33 | ST2 | Increases GVHD via augmentation of Type 1 Immunity Supports protection of HTx via Treg expansion |
(25) (26, 29) |
Cytosolic Materials | |||
Heme | TLR4 | Implicated in innate immune cell activation leading to increased alloimmune responses |
(12) (19) |
Haptoglobin | MyD88-dependent Receptor |
Donor Haptoglobin Activates DC to stimulate allograft rejection |
(13) |
Mitochondria | Formyl Peptide Receptor-1; TLR9 |
Proposed to activate innate responses after Tx |
(11) |
ATP | P2X7 | Promotes GVHD | (15) |
Heat Shock Proteins (HSP) | Promotes alloreactive T cell proliferation and GVHD Modulation of Treg may be protective against I/R |
(15) (48) |
|
Extracellular Matrix Materials | |||
Heparan Sulfate | TLR4-My88 | Mediates activation of DC to promote alloimmune responses |
(15) |
Hyaluronan | TLR2/4-My88 | Low molecular weight hyaluronan degradation products activates APC to stimulate chemokine and cytokine production, which drives alloimmunity High molecular weight hyaluronan protects against epithelial cell apoptosis and attenuates allograft inflammation. |
(51) (52) (53) (50) (51) (53) |