Stabilin-1 mediates phosphatidylserine-dependent clearance of cell cropses in alternatively activated macrophages

Seung Yoon Park, Mi Yeon Jung, Sung Jin Lee, Kae Bok Kang, Alexei Gratchev, Vladimir Riabov, Julia Kzhyshkowska, In San Kim

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85 Citations (Scopus)

Abstract

Stabilin-1 is specifically expressed in alternatively activated macrophages. These macrophages participate in anti-inflammatory and healing processes, and display a high phagocytic capacity. In this study, we provide evidence that stabilin-1 is a membrane receptor that performs a crucial function in the clearance of cell corpses. Stabilin-1 is expressed on the cell surface of alternatively activated macrophages and is recruited to the sites of recognition and engulfment of apoptotic bodies, as well as to early phagosomes. Blocking stabilin-1 in macrophages results in defective engulfment of aged red blood cells. Ectopic expression of stabilin-1 induces the binding and engulfment of aged cells in mouse fibroblast L cells. The binding and phagocytosis are dependent on phosphatidylserine (PS), which is well known as an engulfing ligand. Furthermore, using PS-coated beads, we demonstrate that PS directly interacts with stabilin-1 and is sufficient for stabilin-1-mediated phagocytosis. EGF-like domain repeat in stabilin-1 is responsible for PS recognition and binding. Thus, our results demonstrate that stabilin-1, found on alternatively activated macrophages, is a phagocytic receptor mediating the clearance of apoptotic cells in a PS-dependent manner. Therefore, this protein might play an important role in the maintenance of tissue homeostasis and prevention of autoimmunity.

Original languageEnglish
Pages (from-to)3365-3373
Number of pages9
JournalJournal of Cell Science
Volume122
Issue number18
DOIs
Publication statusPublished - 2009 Sep 15

Keywords

  • Aged RBC
  • Apoptotic cells
  • Macrophages
  • Phagocytosis
  • Stabilin-1

ASJC Scopus subject areas

  • Cell Biology

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    Park, S. Y., Jung, M. Y., Lee, S. J., Kang, K. B., Gratchev, A., Riabov, V., Kzhyshkowska, J., & Kim, I. S. (2009). Stabilin-1 mediates phosphatidylserine-dependent clearance of cell cropses in alternatively activated macrophages. Journal of Cell Science, 122(18), 3365-3373. https://doi.org/10.1242/jcs.049569