Signal Regulatory Protein α Negatively Regulates β2 Integrin-Mediated Monocyte Adhesion, Transendothelial Migration and Phagocytosis

Background: Signal regulate protein alpha (SIRP alpha) is involved in many functional aspects of monocytes. Here we investigate the role of SIRP alpha 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 SIRP alpha expression but an increase of beta(2) integrin cell surface expression and beta(2) integrin-mediated adhesion to tumor necrosis factor-alpha (TNF alpha)-stimulated human microvascular endothelial cell (HMEC-1) monolayers. In contrast, SIRP alpha 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. SIRP alpha overexpression reduced beta(2) integrin-mediated firm adhesion of THP-1 cells to either TNF alpha-stimulated HMEC-1 monolayers or to immobilized intercellular adhesion molecule-1 (ICAM-1). SIRP alpha overexpression also reduced MCP-1-initiated migration of THP-1 cells across TNF alpha-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 SIRP alpha overexpression. Conclusions/Significance: SIRP alpha 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.