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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.

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Related in: MedlinePlus

SIRPα overexpression in THP-1 cells impairs cell phagocytic function.Fluorescently labeled bacteria were incubated with SIRPα– or mock–transfected THP-1 cells for 3 h. A: Images of phagocytosis of bacteria by THP-1 cells; B: Quantitative analysis of bacteria phagocytosis by THP-1 cells. Bar = 20 µm. All data are mean±SD (n = 4) of four independent experiments.
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pone-0003291-g006: SIRPα overexpression in THP-1 cells impairs cell phagocytic function.Fluorescently labeled bacteria were incubated with SIRPα– or mock–transfected THP-1 cells for 3 h. A: Images of phagocytosis of bacteria by THP-1 cells; B: Quantitative analysis of bacteria phagocytosis by THP-1 cells. Bar = 20 µm. All data are mean±SD (n = 4) of four independent experiments.

Mentions: The phagocytic function of THP-1 cells is also dependent on β2 integrins [40], [41], [42]. Next we examined the effect of SIRPα overexpression on the capacity of THP-1 cells to engulf fluorescein–labeled E. coli K12 bioparticles. As shown by confocal images in Figure 6A, the mock-transfected THP-1 cells showed a significant phagocytosis of fluorescein–conjugated bacteria particles after 3 h incubation (Fig. 6A, arrows), while in SIRPα–transfected THP-1 cells, uptake of fluorescein–conjugated bacteria particles was strongly reduced. The quantitative analysis of uptaking fluorescein–conjugated bacteria particles by THP-1 cells was shown in Figure 6B. Taken together, these results clearly show that SIRPα overexpression in THP-1 cells reduces various inflammatory responses mediated by leukocyte β2 integrins.


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 in THP-1 cells impairs cell phagocytic function.Fluorescently labeled bacteria were incubated with SIRPα– or mock–transfected THP-1 cells for 3 h. A: Images of phagocytosis of bacteria by THP-1 cells; B: Quantitative analysis of bacteria phagocytosis by THP-1 cells. Bar = 20 µm. All data are mean±SD (n = 4) of four independent experiments.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0003291-g006: SIRPα overexpression in THP-1 cells impairs cell phagocytic function.Fluorescently labeled bacteria were incubated with SIRPα– or mock–transfected THP-1 cells for 3 h. A: Images of phagocytosis of bacteria by THP-1 cells; B: Quantitative analysis of bacteria phagocytosis by THP-1 cells. Bar = 20 µm. All data are mean±SD (n = 4) of four independent experiments.
Mentions: The phagocytic function of THP-1 cells is also dependent on β2 integrins [40], [41], [42]. Next we examined the effect of SIRPα overexpression on the capacity of THP-1 cells to engulf fluorescein–labeled E. coli K12 bioparticles. As shown by confocal images in Figure 6A, the mock-transfected THP-1 cells showed a significant phagocytosis of fluorescein–conjugated bacteria particles after 3 h incubation (Fig. 6A, arrows), while in SIRPα–transfected THP-1 cells, uptake of fluorescein–conjugated bacteria particles was strongly reduced. The quantitative analysis of uptaking fluorescein–conjugated bacteria particles by THP-1 cells was shown in Figure 6B. Taken together, these results clearly show that SIRPα overexpression in THP-1 cells reduces various inflammatory responses mediated by leukocyte β2 integrins.

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