Resolution of post-lung transplant ischemia-reperfusion injury is modulated via Resolvin D1-FPR2 and Maresin 1-LGR6 signaling

Lipoxin A4/FPR2 signaling mitigates ferroptosis of alveolar epithelial cells via NRF2-dependent pathway during lung ischemia-reperfusion injury

“…Specific SPMs have been demonstrated to have remarkable anti-inflammatory properties leading to inflammation-resolution by regulating the activation of immune cells, and mediating the crosstalk with parenchymal cells to limit the injury cascade (23). Previously, we have shown that there is a significant increase in LxA 4 levels in human BAL from post LTx patients suggesting that LxA 4 plays an important role in endogenous mechanisms that facilitate resolution of inflammation (4). The results reported in the current study describe a previously uncharacterized role of LxA 4 in attenuating ferroptosis after lung IRI via mechanistic signaling on ATII cells.…”

“…Post LTx ischemia–reperfusion injury (IRI), which occurs during the process of donor lung preservation and transplantation, contributes to the development of primary graft dysfunction (PGD) and chronic lung allograft dysfunction (CLAD) (3). During IRI, the endogenous resolution of inflammation mechanisms become compromised, leading to prolonged and dysregulated inflammation (4). Hallmarks and sequalae of lung IRI include increased acute innate immunity responses and oxidative stress resulting in inflammation, vascular permeability, pulmonary edema, alveolar damage and ultimately lung dysfunction (5).…”

“…Our previous study determined that SPMs such as LxA 4 are significantly and sequentially increased in human post-LTx bronchoalveolar lavage (BAL) samples (4). In this study, we investigated the cell-specific role of ferroptosis in lung IRI and elucidated the effectiveness of LxA 4 to mitigate lung IRI by protecting against ferroptosis-mediated inflammation.…”

Maresin‐1 ameliorates hypertensive vascular remodeling through its receptor LGR6

“…MaR1 can activate LGR6 receptor, thereby promoting phagocyte immunoresolvent functions 15,16 . Furthermore, MaR1/LGR6 signaling can mitigate CXCL1 secretion and alleviate post‐lung transplant ischemia–reperfusion injury in mice 17 . The MaR1/LGR6 axis maintains the balance between pulmonary artery smooth muscle cells (PASMCs) proliferation and apoptosis 18 .…”

“…15,16 Furthermore, MaR1/LGR6 signaling can mitigate CXCL1 secretion and alleviate post-lung transplant ischemiareperfusion injury in mice. 17 The MaR1/LGR6 axis maintains the balance between pulmonary artery smooth muscle cells (PASMCs) proliferation and apoptosis. 18 In addition, LGR6 is required for MaR1 to regulate brown adipose tissue activation and white adipose tissue browning.…”