Mechanism for phosphatidylserine-dependent erythrophagocytosis in mouse liver

Sung Jin Lee, Seung Yoon Park, Mi Yeon Jung, Sang Mun Bae, In-San Kim

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Aged or damaged RBCs are effectively removed from the blood circulation by Kupffer cells in the liver, but little is known regarding the mechanism of the clearance process. Here we show that stabilin-1 and stabilin-2 in hepatic sinusoidal endothelial cells (HSECs) are critical in effectively clearing damaged RBCs in mouse liver. Damaged RBCs and phosphatidylserine (PS)-coated beads were effectively sequestered in the hepatic sinusoid regardless of the presence of Kupffer cells, suggesting a role for HSECs in PS-dependent sequestration of PS-exposed RBCs in the liver. HSECs mediate tethering of damaged RBCs in a PS-dependent manner via stabilin-1 and stabilin-2. In a sinusoid-mimicked coculture system consisting of macrophages layered over HSECs, there was significant enhancement of the phagocytic capacity of macrophages, and this was mediated by stabilin-1 and stabilin-2 in HSECs. Liver-specific knockdown of stabilin-1 and stabilin-2 inhibited the sequestration of damaged RBCs in the hepatic sinusoid and delayed the elimination of damaged cells in an in vivo animal model. Thus, the roles of stabilin-1 and stabilin-2 in hepatic sequestration of PS-exposed RBCs may represent a potential mechanism for the clearance of damaged RBCs by Kupffer cells and for the control of some pathologic conditions such as hemolytic anemia.

Original languageEnglish
Pages (from-to)5215-5223
Number of pages9
JournalBlood
Volume117
Issue number19
DOIs
Publication statusPublished - 2011 May 12
Externally publishedYes

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Phosphatidylserines
Endothelial cells
Liver
Macrophages
Endothelial Cells
Kupffer Cells
Hemodynamics
Animals
Blood Circulation
Hemolytic Anemia
Coculture Techniques
Animal Models

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Mechanism for phosphatidylserine-dependent erythrophagocytosis in mouse liver. / Lee, Sung Jin; Park, Seung Yoon; Jung, Mi Yeon; Bae, Sang Mun; Kim, In-San.

In: Blood, Vol. 117, No. 19, 12.05.2011, p. 5215-5223.

Research output: Contribution to journalArticle

Lee, Sung Jin ; Park, Seung Yoon ; Jung, Mi Yeon ; Bae, Sang Mun ; Kim, In-San. / Mechanism for phosphatidylserine-dependent erythrophagocytosis in mouse liver. In: Blood. 2011 ; Vol. 117, No. 19. pp. 5215-5223.
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