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

Liu DQ, Li LM, Guo YL, Bai R, Wang C, Bian Z, Zhang CY, Zen K - PLoS ONE (2008)

Bottom Line: 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 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.

View Article: PubMed Central - PubMed

Affiliation: Jiangsu Diabetes Research Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.

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.

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.

Show MeSH

Related in: MedlinePlus

SIRPα overexpression reduces the MCP-1–induced migration of THP-1 cells across HMEC-1 monolayers pre-activated with 25 ng/mL TNFα.All data are mean±SD (n = 3) of three independent experiments.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2553263&req=5

pone-0003291-g004: SIRPα overexpression reduces the MCP-1–induced migration of THP-1 cells across HMEC-1 monolayers pre-activated with 25 ng/mL TNFα.All data are mean±SD (n = 3) of three independent experiments.

Mentions: Previous studies have reported that chemokine-mediated activation of β2 integrins was essential for THP-1 cell adhesion and subsequent transmigration through endothelial monolayers [7], [8], [38]. Therefore, the effect of SIRPα overexpression on transendothelial migration (TEM) of THP-1 cells was examined by transmigration assay. In mock-transfected THP-1 cells, MCP-1 triggered strong THP-1 cell migration across HMEC-1 monolayers. As shown in Figure 4, more than 20% of total applied THP-1 cells were migrated across TNFα–activated HMEC-1 monolayers after 3 h incubation. In contrast, MCP-1–triggered transmigration of THP-1 cells that were overexpressed with SIRPα was strongly reduced (Fig. 4). In both mock-transfected and SIRPα overexpressed THP-1 cells, spontaneous migration of THP-1 cells in the absence of MCP-1 was minimal (data not shown).


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

Liu DQ, Li LM, Guo YL, Bai R, Wang C, Bian Z, Zhang CY, Zen K - PLoS ONE (2008)

SIRPα overexpression reduces the MCP-1–induced migration of THP-1 cells across HMEC-1 monolayers pre-activated with 25 ng/mL TNFα.All data are mean±SD (n = 3) of three independent experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2553263&req=5

pone-0003291-g004: SIRPα overexpression reduces the MCP-1–induced migration of THP-1 cells across HMEC-1 monolayers pre-activated with 25 ng/mL TNFα.All data are mean±SD (n = 3) of three independent experiments.
Mentions: Previous studies have reported that chemokine-mediated activation of β2 integrins was essential for THP-1 cell adhesion and subsequent transmigration through endothelial monolayers [7], [8], [38]. Therefore, the effect of SIRPα overexpression on transendothelial migration (TEM) of THP-1 cells was examined by transmigration assay. In mock-transfected THP-1 cells, MCP-1 triggered strong THP-1 cell migration across HMEC-1 monolayers. As shown in Figure 4, more than 20% of total applied THP-1 cells were migrated across TNFα–activated HMEC-1 monolayers after 3 h incubation. In contrast, MCP-1–triggered transmigration of THP-1 cells that were overexpressed with SIRPα was strongly reduced (Fig. 4). In both mock-transfected and SIRPα overexpressed THP-1 cells, spontaneous migration of THP-1 cells in the absence of MCP-1 was minimal (data not shown).

Bottom Line: 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 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.

View Article: PubMed Central - PubMed

Affiliation: Jiangsu Diabetes Research Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.

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.

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.

Show MeSH
Related in: MedlinePlus