Signal regulatory protein alpha negatively regulates beta2 integrin-mediated monocyte adhesion, transendothelial migration and phagocytosis.
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.
Liu
Dan-Qing
DQ
Jiangsu Diabetes Research Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
Li
Li-Min
LM
Guo
Ya-Lan
YL
Bai
Rui
R
Wang
Chen
C
Bian
Zhen
Z
Zhang
Chen-Yu
CY
Zen
Ke
K
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
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