title: Signal regulatory protein alpha negatively regulates beta2 integrin-mediated monocyte adhesion, transendothelial migration and phagocytosis.
abstract: 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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Jiangsu Diabetes Research Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Dan-Qing
authors.initials: DQ
authors.lastname: Liu
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Li
authors.forename: Ya-Lan
authors.initials: YL
authors.lastname: Guo
authors.forename: Rui
authors.initials: R
authors.lastname: Bai
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Bian
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Zhang
authors.forename: Ke
authors.initials: K
authors.lastname: Zen
mesh_terms: D000943:Antigens, Differentiation / Q000378:metabolism / Q000502:physiology*; D050197:Atherosclerosis; D039481:CD11b Antigen / Q000096:biosynthesis; D018821:CD18 Antigens / Q000096:biosynthesis / Q000276:immunology*; D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D008954:Models, Biological; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D010587:Phagocytosis; D011971:Receptors, Immunologic / Q000378:metabolism / Q000502:physiology*; D011994:Recombinant Proteins / Q000737:chemistry
chemical_list: D000943:Antigens, Differentiation; C111835:CCL2 protein, human; D039481:CD11b Antigen; D018821:CD18 Antigens; D018932:Chemokine CCL2; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; C501920:SIRPA protein, human