Modulation of RAGE expression influences the adhesion of red blood cells from diabetic patients.
Atherothrombotic complications are frequent in patients with type 2 diabetes. Red blood cells (RBC) from diabetic patients exhibited an increased adhesion which correlated to the extent of vascular complications. In the present study we have investigated the adhesive interactions of RBCs with endothelium, using flow-based assessments. RBCs and endothelial cells were unstimulated or stimulated using respectively adrenaline and TNFalpha. Adhesion assays were carried-out by drawing the RBC suspension through a glass microcapillary tube precoated by human umbilical vein endothelial cells. These microslides were then incorporated into a controlled flow system equipped with a computerized video-microscopic image analysis. RBCs from diabetic patients bind to endothelial cells and could withstand wall shear stresses above 0.1 Pa. After stimulation by TNFalpha the adhesion was 1.5-fold higher. Blocking experiments demonstrated that the adhesion was mediated by the receptor for AGE (RAGE). Adrenaline-treated RBCs showed a transient increase in adhesion at low shear stresses. Inflammatory mediators or catecholamine amplifying diabetic RBC adhesion may aggravate endothelial cell damages.
Wautier
Marie-Paule
MP
Inserm, U 665, Paris F-75015, France.
Khodabandehlou
Taraneh
T
Le Dévéhat
Claude
C
Wautier
Jean-Luc
JL
D000368:Aged; D002448:Cell Adhesion; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D042783:Endothelial Cells / Q000166:cytology; D004730:Endothelium, Vascular / Q000166:cytology; D004837:Epinephrine / Q000494:pharmacology; D004903:Erythrocyte Aggregation; D004912:Erythrocytes / Q000166:cytology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; D004837:Epinephrine