Macrophagic Stabilin-1 Restored Disruption of Vascular Integrity Caused by Sepsis

Wonhwa Lee, Seung Yoon Park, Youngbum Yoo, Soon Young Kim, Jung Eun Kim, Shin Woo Kim, Young Kyo Seo, Eui Kyun Park, In-San Kim, Jong Sup Bae

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1776-1789
Number of pages14
JournalThrombosis and Haemostasis
Volume118
Issue number10
DOIs
Publication statusPublished - 2018 Jan 1

Keywords

  • efferocytosis
  • phagocytosis
  • sepsis
  • STAB-1
  • vascular integrity

ASJC Scopus subject areas

  • Hematology

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  • Cite this

    Lee, W., Park, S. Y., Yoo, Y., Kim, S. Y., Kim, J. E., Kim, S. W., Seo, Y. K., Park, E. K., Kim, I-S., & Bae, J. S. (2018). Macrophagic Stabilin-1 Restored Disruption of Vascular Integrity Caused by Sepsis. Thrombosis and Haemostasis, 118(10), 1776-1789. https://doi.org/10.1055/s-0038-1669477