Sepsis develops because of overwhel

Sepsis develops because of overwhelming inflammatory responses to bacterial infection, and disrupts vascular integrity. Stabilin-1 (STAB-1) is a phagocytic receptor, whichmediates efferocytosis in a phosphatidylserine (PS)-dependent manner. STAB-1 isexpected to play important roles in efferocytosis during sepsis. Here, we determinedthe role of STAB-1 in maintaining and restoring vascular integrity. Macrophages andvascular endothelial cells were used to assess the effect of STAB-1 on survival rate,phagocytic activity, vascular permeability and transendothelial migration (TEM).Additionally, we investigated whether the high-mobility group box 1 (HMGB1)-receptorfor advanced glycated end products complex interfered with the binding of Stab1 to PS.Mortality rate was higher in the Stab1-knockout mice than in the wild-type mice, andSTAB-1 deficiency was related to reduced macrophage-mediated efferocytosis and thedisruption of vascular integrity, which increased vascular permeability, and enhancedTEM. STAB-1 deficiency promoted lung injury, and elevated the expression of sepsismarkers. The exogenous application of the anti-HMGB1 neutralizing antibodyimproved efferocytosis, vascular integrity and survival rate in sepsis. Collectively,our findings indicated that STAB-1 regulated and maintained vascular integrity throughthe clearance of infected apoptotic endothelial cells. Moreover, our results suggestedthat interventions targeting vascular integrity by STAB-1 signalling are promisingtherapeutic approaches to sepsis.