Heparin-binding protein (HBP), as a granule protein secreted by polymorphonuclear neutrophils, participates in the pathophysiological process of sepsis. It has been reported that HBP is a biomarker of sepsis related to the severity of septic shock and organ dysfunction. HBP binds to vascular endothelial cells as a primary target site. However, it is still unclear whether HBP-binding protein receptors exist on the surface of endothelial cells. The effect of HBP on vascular permeability in sepsis and its mechanism needs to be explored. We conducted in vivo and in vitro studies and demonstrated that HBP binds to transforming growth factor-β receptor type 2 (TGF-β-R2) as a ligand. Glutathione S-transferase pull-down analysis revealed that HBP mainly interacts with the extracellular domain of TGF-β-R2. HBP induces acute lung injury and vascular leakage via activation of the TGF-β/SMAD2/3 signaling pathway. A permeability assay suggested that TGF-β-R2 is necessary for HBP-induced increased permeability. We also defined the role of HBP and its potential membrane receptor TGF-β-R2 in the blood-gas barrier in the pathogenesis of HBP-related acute lung injury.
Keywords: acute lung injury; heparin-binding protein (HBP); infection; transforming growth factor-β receptor type 2 (TGF-β-R2); vascular permeability.
© 2022 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.