Human intrahepatic biliary epithelial cells engulf blebs from their apoptotic peers

Clin Exp Immunol. 2013 Apr;172(1):95-103. doi: 10.1111/cei.12046.

Abstract

The phagocytic clearance of apoptotic cells is critical for tissue homeostasis; a number of non-professional phagocytic cells, including epithelial cells, can both take up and process apoptotic bodies, including the release of anti-inflammatory mediators. These observations are particularly important in the case of human intrahepatic biliary cells (HiBEC), because such cells are themselves a target of destruction in primary biliary cirrhosis, the human autoimmune disease. To address the apoptotic ability of HiBECs, we have focused on their ability to phagocytize apoptotic blebs from autologous HiBECs. In this study we report that HiBEC cells demonstrate phagocytic function from autologous HiBEC peers accompanied by up-regulation of the chemokines CCL2 [monocyte chemotactic protein-1 (MCP-1)] and CXCL8 [interleukin (IL)-8]. In particular, HiBEC cells express the phagocytosis-related receptor phosphatidylserine receptors (PSR), implying that HiBECs function through the 'eat-me' signal phosphatidylserine expressed by apoptotic cells. Indeed, although HiBEC cells acquire antigen-presenting cell (APC) function, they do not change the expression of classic APC function surface markers after engulfment of blebs, both with and without the presence of Toll-like receptor (TLR) stimulation. These results are important not only for understanding of the normal physiological function of HiBECs, but also explain the inflammatory potential and reduced clearance of HiBEC cells following the inflammatory cascade in primary biliary cirrhosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Bile Acids and Salts / pharmacology
  • Bile Ducts, Intrahepatic / cytology
  • Bile Ducts, Intrahepatic / immunology*
  • Cells, Cultured
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / immunology
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Epithelial Cells / immunology*
  • Gene Expression
  • Humans
  • Interleukin-8 / genetics
  • Interleukin-8 / immunology
  • Lipopolysaccharides / pharmacology
  • Liver Cirrhosis, Biliary / immunology
  • Liver Cirrhosis, Biliary / pathology
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / immunology*
  • Mice
  • Phagocytosis*
  • Phosphatidylserines / immunology
  • Phosphatidylserines / metabolism
  • Poly I-C / pharmacology
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / immunology
  • Signal Transduction
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / immunology
  • Up-Regulation

Substances

  • Bile Acids and Salts
  • CCL2 protein, human
  • CXCL8 protein, human
  • Chemokine CCL2
  • Interleukin-8
  • Lipopolysaccharides
  • Phosphatidylserines
  • Receptors, Cell Surface
  • Toll-Like Receptors
  • phosphatidylserine receptor
  • Poly I-C