Lee, Wonhwa Park, Seung-Yoon Yoo, Youngbum Kim, Soon-Young Kim, Jung-Eun Kim, Shin-Woo Seo, Young-Kyo Park, Eui Kyun Kim, In-San Bae, Jong-Sup 2024-01-19T21:34:15Z 2024-01-19T21:34:15Z 2021-09-04 2018-10 0340-6245 https://pubs.kist.re.kr/handle/201004/120863 Sepsis develops because of overwhelming inflammatory responses to bacterial infection, and disrupts vascular integrity. Stabilin-1 (STAB-1) is a phagocytic receptor, which mediates efferocytosis in a phosphatidylserine (PS)-dependent manner. STAB-1 is expected to play important roles in efferocytosis during sepsis. Here, we determined the role of STAB-1 in maintaining and restoring vascular integrity. Macrophages and vascular 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)-receptor for 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, and STAB-1 deficiency was related to reduced macrophage-mediated efferocytosis and the disruption of vascular integrity, which increased vascular permeability, and enhanced TEM. STAB-1 deficiency promoted lung injury, and elevated the expression of sepsis markers. The exogenous application of the anti-HMGB1 neutralizing antibody improved efferocytosis, vascular integrity and survival rate in sepsis. Collectively, our findings indicated that STAB-1 regulated and maintained vascular integrity through the clearance of infected apoptotic endothelial cells. Moreover, our results suggested that interventions targeting vascular integrity by STAB-1 signalling are promising therapeutic approaches to sepsis. English GEORG THIEME VERLAG KG ACUTE LUNG INJURY APOPTOTIC CELLS ENDOTHELIAL-CELLS SEPTIC SHOCK PERITONEAL-MACROPHAGES SCAVENGER RECEPTOR ORGAN FAILURE HOST-DEFENSE PROTEIN-C IN-VITRO Macrophagic Stabilin-1 Restored Disruption of Vascular Integrity Caused by Sepsis Article 10.1055/s-0038-1669477 1 THROMBOSIS AND HAEMOSTASIS, v.118, no.10, pp.1776 - 1789 THROMBOSIS AND HAEMOSTASIS 118 10 1776 1789 scie scopus 000446519900011 2-s2.0-85054073221 Hematology Peripheral Vascular Disease Hematology Cardiovascular System & Cardiology Article ACUTE LUNG INJURY APOPTOTIC CELLS ENDOTHELIAL-CELLS SEPTIC SHOCK PERITONEAL-MACROPHAGES SCAVENGER RECEPTOR ORGAN FAILURE HOST-DEFENSE PROTEIN-C IN-VITRO STAB-1 efferocytosis sepsis vascular integrity phagocytosis