caa a22 4500 475772431 CHVBK 20180406123621.0 cr unu---uuuuu 170329e20000801xx s 000 0 eng 10.1007/s001250051487 doi (NATIONALLICENCE)springer-10.1007/s001250051487 Glucose-induced loss of glycosyl-phosphatidylinositol-anchored membrane regulators of complement activation (CD59, CD55) by in vitro cultured human umbilical vein endothelial cells [Elektronische Daten] [A. Accardo-Palumbo, G. Triolo, G. Colonna-Romano, M. Potestio, M. Carbone, A. Ferrante, E. Giardina, G. Caimi, G. Triolo] Aims/hypothesis. This study examines whether increased glucose concentrations are responsible for a decreased expression of membrane regulators of complement activation molecules. The effect of high glucose in determining an increase in membrane attack complex deposition on endothelial cells was also investigated. Methods. Endothelial cells were isolated from umbilical cord tissue, cultured in the presence of increased concentrations of glucose, and the expression of CD46, CD55, and CD59 was detected by ELISA (enzyme-linked immunosorbent assay) and by flow cytometry. Glucose-treated endothelial cells were also incubated with antiendothelial cell antibodies and fresh complement to assess the amount of membrane attack complex formation. Results. High concentrations of glucose decreased the expression of CD59 and CD55 by endothelial cells in a time-dependent and glucose concentration-dependent manner without affecting CD46 expression. High concentrations of soluble CD59 were found in the supernatants of cells treated with high glucose. The decrease in CD59 expression induced by high glucose concentrations was reversed by coincubation of cells with a calcium channel blocking agent (Verapamil). All of these effects were not reproduced by osmotic control media. Cells treated with concentrations of high glucose were more susceptible to complement activation and membrane attack complex formation after exposure to antiendothelial cell antibodies. Conclusion/Interpretation. We speculate that hyperglycaemia could directly contribute to a loss of CD59 and CD55 molecules through a calcium-dependent phosphoinositol-specific phospholipase C activation and subsequent regulation of cell wall expression of GPI-anchored proteins. This phenomenon could facilitate the activation of a complement pathway and could play a part in the aetiology of endothelial dysfunction in diabetes. [Diabetologia (2000) 43: 1039-1047] Springer-Verlag Berlin Heidelberg, 2000 Keywords CD59 nationallicence CD55 nationallicence CD46 nationallicence endothelial cells nationallicence glucose nationallicence diabetes mellitus nationallicence vascular complications nationallicence MAC nationallicence Accardo-Palumbo A. Department of Internal Medicine, Section of Clinical Immunology, Rheumatology and Allergy, University of Palermo, Palermo, Italy, IT aut Triolo G. Department of Internal Medicine, Section of Clinical Immunology, Rheumatology and Allergy, University of Palermo, Palermo, Italy, IT aut Colonna-Romano G. Department of Pathology, University of Palermo, Palermo, Italy, IT aut Potestio M. Department of Pathology, University of Palermo, Palermo, Italy, IT aut Carbone M. Department of Internal Medicine, Section of Clinical Immunology, Rheumatology and Allergy, University of Palermo, Palermo, Italy, IT aut Ferrante A. Department of Internal Medicine, Section of Clinical Immunology, Rheumatology and Allergy, University of Palermo, Palermo, Italy, IT aut Giardina E. Department of Internal Medicine, Section of Clinical Immunology, Rheumatology and Allergy, University of Palermo, Palermo, Italy, IT aut Caimi G. Department of Internal Medicine, Section of Clinical Methodology, University of Palermo, Palermo, Italy, IT aut https://doi.org/10.1007/s001250051487 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250051487 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Accardo-Palumbo A. Department of Internal Medicine, Section of Clinical Immunology, Rheumatology and Allergy, University of Palermo, Palermo, Italy, IT aut NATIONALLICENCE 700 1- Triolo G. Department of Internal Medicine, Section of Clinical Immunology, Rheumatology and Allergy, University of Palermo, Palermo, Italy, IT aut NATIONALLICENCE 700 1- Colonna-Romano G. Department of Pathology, University of Palermo, Palermo, Italy, IT aut NATIONALLICENCE 700 1- Potestio M. Department of Pathology, University of Palermo, Palermo, Italy, IT aut NATIONALLICENCE 700 1- Carbone M. Department of Internal Medicine, Section of Clinical Immunology, Rheumatology and Allergy, University of Palermo, Palermo, Italy, IT aut NATIONALLICENCE 700 1- Ferrante A. Department of Internal Medicine, Section of Clinical Immunology, Rheumatology and Allergy, University of Palermo, Palermo, Italy, IT aut NATIONALLICENCE 700 1- Giardina E. Department of Internal Medicine, Section of Clinical Immunology, Rheumatology and Allergy, University of Palermo, Palermo, Italy, IT aut NATIONALLICENCE 700 1- Caimi G. Department of Internal Medicine, Section of Clinical Methodology, University of Palermo, Palermo, Italy, IT aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer