High glucose induces enhanced monocyte adhesion to valvular endothelial cells via a mechanism involving ICAM-1, VCAM-1 and CD18.
Upon induction of experimental hyperglycemia (i.e. diabetes) pathological modifications are early detected (approximately 7 days) at the level of the cardiac valves leading rapidly to the development of valvular atheroma. Monocyte adhesion to the vascular endothelium is one of the initial event at the onset of atherosclerosis. We questioned whether high glucose enhances monocyte adhesion to the valvular endothelial cells (VEC) so as to explain, in part, the accelerated atheroma formation that occur in diabetic conditions. To this purpose we compared the adhesion of monocytes to VEC cultured in 5.5 mM (normal) glucose (NG) or in 33 mM (high) glucose (HG) or in high mannitol (HM) (27.5 mM mannitol plus 5.5 mM glucose), a concentration known to simulate the hyperosmolar effect of high glucose. After incubation for 30 min at 37 degrees C, the adhesion of monocyte cell line (U937 cells) to VEC was quantitated by a fluorimetric assay or by direct counting. Statistical data showed a significant increased adhesion of monocytes to VEC grown in HG (up to 4 fold) or in HM (up to 2.7) when compared to normal conditions. Using a battery of specific monoclonal antibodies molecules it was found that the increased adhesion of monocytes to VEC grown in high glucose was specifically inhibited (p < 0.05) by anti-ICAM-1, anti-VCAM-1 and anti-CD18 monoclonal antibodies. Together, the results indicate that high glucose induces enhanced monocyte adhesion to VEC via a mechanism involving in part an osmotic effect and mainly the cell adhesion molecules: ICAM-1, VCAM-1 and CD18.
Manduteanu
I
I
Institute for Cellular Biology and Pathology N. Simionescu, Bucharest, Romania.
Voinea
M
M
Serban
G
G
Simionescu
M
M
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D018821:CD18 Antigens / Q000378:metabolism*; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000648:ultrastructure; D004797:Enzyme-Linked Immunosorbent Assay; D005947:Glucose / Q000494:pharmacology*; D006351:Heart Valves / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007365:Intercellular Junctions / Q000187:drug effects / Q000648:ultrastructure; D008353:Mannitol / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism* / Q000648:ultrastructure; D009994:Osmolar Concentration; D020298:U937 Cells / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D019138:Antibodies, Blocking; D018821:CD18 Antigens; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D008353:Mannitol; D005947:Glucose