Signal regulatory protein alpha negatively regulates beta2 integrin-mediated monocyte adhesion, transendothelial migration and phagocytosis

PLoS One. 2008 Sep 29;3(9):e3291. doi: 10.1371/journal.pone.0003291.


Background: Signal regulate protein alpha (SIRPalpha) is involved in many functional aspects of monocytes. Here we investigate the role of SIRPalpha in regulating beta(2) integrin-mediated monocyte adhesion, transendothelial migration (TEM) and phagocytosis.

Methodology/principal findings: THP-1 monocytes/macropahges treated with advanced glycation end products (AGEs) resulted in a decrease of SIRPalpha expression but an increase of beta(2) integrin cell surface expression and beta(2) integrin-mediated adhesion to tumor necrosis factor-alpha (TNFalpha)-stimulated human microvascular endothelial cell (HMEC-1) monolayers. In contrast, SIRPalpha overexpression in THP-1 cells showed a significant less monocyte chemotactic protein-1 (MCP-1)-triggered cell surface expression of beta(2) integrins, in particular CD11b/CD18. SIRPalpha overexpression reduced beta(2) integrin-mediated firm adhesion of THP-1 cells to either TNFalpha-stimulated HMEC-1 monolayers or to immobilized intercellular adhesion molecule-1 (ICAM-1). SIRPalpha overexpression also reduced MCP-1-initiated migration of THP-1 cells across TNFalpha-stimulated HMEC-1 monolayers. Furthermore, beta(2) integrin-mediated THP-1 cell spreading and actin polymerization in response to MCP-1, and phagocytosis of bacteria were both inhibited by SIRPalpha overexpression.

Conclusions/significance: SIRPalpha negatively regulates beta(2) integrin-mediated monocyte adhesion, transendothelial migration and phagocytosis, thus may serve as a critical molecule in preventing excessive activation and accumulation of monocytes in the arterial wall during early stage of atherosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Differentiation / metabolism
  • Antigens, Differentiation / physiology*
  • Atherosclerosis
  • CD11b Antigen / biosynthesis
  • CD18 Antigens / biosynthesis
  • CD18 Antigens / immunology*
  • Cell Adhesion
  • Cell Line
  • Cell Movement
  • Chemokine CCL2 / metabolism
  • Down-Regulation*
  • Humans
  • Models, Biological
  • Monocytes / cytology
  • Monocytes / immunology*
  • Phagocytosis
  • Receptors, Immunologic / metabolism
  • Receptors, Immunologic / physiology*
  • Recombinant Proteins / chemistry


  • Antigens, Differentiation
  • CCL2 protein, human
  • CD11b Antigen
  • CD18 Antigens
  • Chemokine CCL2
  • Receptors, Immunologic
  • Recombinant Proteins
  • SIRPA protein, human