Platelet-Specific Deletion of TGF-β1 Impairs Septic Thrombosis in Mice—Brief Report

BACKGROUND: Sepsis is featured as a systemic inflammation and thrombosis induced by infection. TGF-β (transforming growth factor-β) 1 is mainly secreted from platelets and plays a role in immune response and inflammation. Whether platelet-derived TGF-β1 participates in sepsis remains unclear. This study intends to investigate its role in sepsis in mice. METHODS: Platelet-specific TGF-β1 knockout mice received cecal ligation and puncture surgery to induce sepsis followed by the analysis of survival time, platelets number, pathology changes of lung and liver, liver function, the recruitment of platelets, neutrophils and monocytes, and neutrophil extracellular traps' formation. In addition, adoptive transfer of wild-type platelets into platelet-specific TGF-β1 knockout mice was performed to further evaluate the role of TGF-β1 in the pathogenesis of sepsis. RESULTS: TGF-β1 level was gradually increased in the lung during the progress of sepsis, and platelets are the major source of the elevated TGF-β1 level in the lung after sepsis. Deficiency of platelet-derived TGF-β1 prolonged the survival of sepsis mice, inhibited the drop of platelet number and bacterial growth, impaired the thrombus formation in the lung and liver, and improved liver function. In addition, platelet TGF-β1 deficiency also decreased the recruitment of neutrophils and monocytes to the lung and impaired neutrophil extracellular trap formation. However, the adoptive transfer of normal platelets to platelet-specific TGF-β1 knockout mice significantly reduced the number of circulating platelets, increased thrombosis in the lung and liver, and promoted the neutrophil extracellular trap formation. CONCLUSIONS: Deficiency of platelet-derived TGF-β1 inhibits septic thrombosis and prolongs survival time, indicating that it might be a novel therapeutic target for the treatment of sepsis.