Binding of monocytes from normolipidemic hyperglycemic patients with type 1 diabetes to endothelial cells is increased in vitro.
Increased endothelial binding and emigration of monocytes play a dominant role in the pathogenesis of atherosclerosis in diabetes mellitus. Previous studies revealed that hyperlipidemia correlates with monocyte binding in vitro. The aim of this study was to characterize the monocyte-endothelial interaction of leucocytes of hyperglycemic patients with type 1 diabetes but lacking hyperlipidemia. We isolated monocytes from healthy controls and normolipidemic type 1 diabetes patients with elevated levels of HbA1c and quantified monocyte binding by an immunoilluminometric cell adhesion assay. Purity of isolated monocytes was at least 98%. Endothelial binding of monocytes from patients with type 1 diabetes was found to be significantly increased compared to controls (19.2 +/- 3.9% vs. 14.9 +/- 3.5%). This difference of monocyte binding remained unchanged if the endothelial cells were stimulated with 27.7 mmol/l glucose for seven days prior to adhesion studies (31.5 +/- 4.9% in diabetes patients vs. 25.8 +/- 4.1% in controls) whereby monocyte binding markedly increased under these hyperglycemic conditions. Furthermore, an increased CD11b expression could be demonstrated on monocytes of normolipidemic hyperglycemic type 1 diabetes patients. Thus, we suggest that hyperglycemia per se may contribute to increased monocyte binding to endothelial cells by promoting leucocyte integrin expression. Recently performed studies of our group strengthen the hypothesis that this monocyte activation is mediated by stimulation of the beta-isoform of proteinkinase C.
Kunt
T
T
Department of Internal Medicine and Endocrinology, University of Mainz, Germany. endokrin@mail.uni-mainz.de
Forst
T
T
Früh
B
B
Flohr
T
T
Schneider
S
S
Harzer
O
O
Pfützner
A
A
Engelbach
M
M
Löbig
M
M
Beyer
J
J
D000328:Adult; D000911:Antibodies, Monoclonal; D001161:Arteriosclerosis / Q000150:complications* / Q000503:physiopathology; D018845:CD11 Antigens / Q000097:blood; D002448:Cell Adhesion / Q000502:physiology; D002452:Cell Count; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D005947:Glucose / Q000502:physiology; D006801:Humans; D006943:Hyperglycemia / Q000150:complications* / Q000503:physiopathology; D018189:Immunomagnetic Separation; D008163:Luminescent Measurements; D008297:Male; D009000:Monocytes / Q000502:physiology; D015999:Multivariate Analysis; D012044:Regression Analysis
D000911:Antibodies, Monoclonal; D018845:CD11 Antigens; D005947:Glucose