Abstract Number: PB1838
Meeting: ISTH 2020 Congress
Background: Mechanisms of hepatic ischemia-reperfusion injury (IRI), caused by liver surgery, transplantation and trauma, remain unclear and therapy is limited. IRI is characterized by inflammatory cell infiltration and parenchymal cell injury. The tissue damage can be limited by prompt removal of accumulated leukocytes restoring homeostasis by properly completed resolution of inflammation. This phase of inflammation is a biochemical and metabolic process orchestrating the function and migration of immune cells resulting in correct host defense. Impaired resolution disturbs tissue integrity leading to organ failure. Platelets play an immunomodulatory role during onset of liver IRI by interacting with hepatic sinusoidal endothelium and promoting the recruitment of proinflammatory cells. Its role in resolving processes has not been studied yet.
Aims: We aimed to unravel the properties of platelets in hepatic IRI in the resolution phase of inflammation and restoration of homeostasis.
Methods: Human PBMC were stimulated with GM-CSF and challenged with platelets and TNF-α. M1/M2 markers were analyzed by qRT-PCR.
The hepatic IRI C57BL/6 mice were treated with platelet-depleting anti-GPIbα antibody or IgG control. Leukocytes were assessed by flow cytometry; serum was analyzed for liver injury markers; proresolving lipid mediators and its derivates were measured by LC-MS/MS.
Results: We showed that platelets control the phenotypic polarization of macrophages by shifting them from proinflammatory M1 to the anti-inflammatory M2 phenotype depending on stimuli.
We demonstrated sustained proinflammatory state in platelet depleted hepatic IRI mouse model with augmented infiltration of PMN with decreased clearance of apoptotic cells.
Conclusions: Our results reveal dual role of platelets orchestrating leukocyte infiltration in early phases and supporting resolution at later stages of liver inflammation. Further studies will elucidate platelets’ impact on tissue regeneration, its signaling events and link to specialized lipid mediators. Thus, platelets and its metabolites are potential therapeutic targets modulating the outcome of liver IRI and tissue regeneration.
To cite this abstract in AMA style:Stefańczyk SA, Giera M, Stegner D, Körner A, Mirakaj V. Platelets in Resolution of Liver Inflammation and Tissue Regeneration [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/platelets-in-resolution-of-liver-inflammation-and-tissue-regeneration/. Accessed May 6, 2021.
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