Direct modulatory effect of C-reactive protein on primary human monocyte adhesion to human endothelial cells.
C-reactive protein (CRP) is the prototypic acute phase serum protein in humans. The effects of CRP on primary human monocyte adhesion molecule expression and interaction with the endothelium have not been studied. Herein, we describe an investigation into the phenotypic and functional consequences of CRP binding to peripheral blood monocytes ex vivo. Peripheral whole blood was collected from healthy, non-smoking males. Mononuclear cells (MNC) and monocytes were isolated by differential centrifugation using lymphoprep and Dynal negative isolation kit, respectively. Cells were exposed to CRP from 0 to 250 micro g/ml for 0-60 min at 37 degrees C and analysed for (a) CD11b, PECAM-1 (CD31) and CD32 expression by flow cytometry and (b) adhesion to LPS (1 micro g/ml; 0-24 h) treated human umbilical vein endothelial cells (HUVEC). CD14+ monocyte expression of CD11b increased significantly up to twofold when exposed to CRP, compared to controls. There was no significant difference in CD32 expression, whereas CD31 expression decreased after exposure to CRP. CRP treatment of monocytes inhibited their adhesion to early LPS-activated HUVEC (0-5 h). However, the adhesion of CRP-treated monocytes to HUVEC was significantly greater to late activation antigens on HUVEC (24 h, LPS) compared to controls. We have shown that CRP can affect monocyte activation ex vivo and induce phenotypic changes that result in an altered recruitment to endothelial cells. This study provides the first evidence for a further role for C-reactive protein in both monocyte activation and adhesion, which may be of importance during an inflammatory event.
Woollard
K J
KJ
Pharmacology Research Group, Aston University, Aston Triangle, Birmingham, UK.
Phillips
D C
DC
Griffiths
H R
HR
D000906:Antibodies / Q000494:pharmacology; D002097:C-Reactive Protein / Q000494:pharmacology*; D039481:CD11b Antigen / Q000378:metabolism; D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D009000:Monocytes / Q000276:immunology*; D010641:Phenotype; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D017452:Receptors, IgG / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism
D000906:Antibodies; D039481:CD11b Antigen; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D017452:Receptors, IgG; D002097:C-Reactive Protein