Heparan sulfate on activated glomerular endothelial cells and exogenous heparinoids influence the rolling and adhesion of leucocytes

• Published in: Nephrology, dialysis, transplantation Vol. 22; no. 4; pp. 1070 - 1077
• Main Authors: Rops, Angelique L., Jacobs, Cor W., Linssen, Peter C., Boezeman, Jan B., Lensen, Joost F., Wijnhoven, Tessa J., van den Heuvel, Lambert P., van Kuppevelt, Toin H., van der Vlag, Johan, Berden, Jo H.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.04.2007; Oxford Publishing Limited (England)
• Subjects: adhesion of leucocytes; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Anticoagulants - pharmacology; Biological and medical sciences; Cell Adhesion - drug effects; Cell Communication - drug effects; Cell Line; Cell Movement - drug effects; Emergency and intensive care: renal failure. Dialysis management; Endothelium - drug effects; Endothelium - physiology; Fibrinolytic Agents - pharmacology; glomerular endothelial cells; Glomerulonephritis; heparin; Heparin - pharmacology; Heparin, Low-Molecular-Weight - pharmacology; Heparinoids - pharmacology; Heparitin Sulfate - pharmacology; Intensive care medicine; Investigative techniques, diagnostic techniques (general aspects); Kidney Glomerulus - cytology; Kidney Glomerulus - drug effects; Leukocytes - cytology; Leukocytes - drug effects; low molecular weight heparin; Medical sciences; Mice; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; rolling of leucocytes; Tumor Necrosis Factor-alpha - pharmacology; Urinary system; heparin; rolling of leucocytes; low molecular weight heparin; glomerular endothelial cells; adhesion of leucocytes; glomerulonephritis; Kidney disease; Glomerulonephritis; Endothelial cell; Urinary system disease; Hemodialysis; Low molecular weight heparin; Anticoagulant; Sulfates; Dalteparin sodium; Extrarenal dialysis; Renal failure
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfl801

Background. Proliferative glomerulonephritides are characterized by the influx of leucocytes. Heparan sulfate (HS) plays an important role in the recruitment, rolling and firm adhesion of leucocytes to activated endothelium. Recently, we have shown the importance of HS on activated mouse glomerular endothelial cells (mGEnC-1) for the firm adhesion of leucocytes in a static adhesion assay. In the present study, we evaluated the role of HS on glomerular endothelial cells and the effect of adding heparinoids on the leucocyte–glomerular endothelium interaction under dynamic flow conditions. Methods. The number of rolling and firmly adhering leucocytes, and the rolling velocity of leucocytes was determined on a monolayer of unactivated or TNF-α-activated mGEnC-1 under dynamic flow conditions using physiological relevant shear stress rates in a flow chamber system. Furthermore, the effects of removal of HS on TNF-α-activated mGEnC-1 by heparinase III treatment, and of different concentrations of heparin, tinzaparin and HS, on the rolling and adhesion of leucocytes were evaluated. Results. At the calculated physiological shear stress rate of 0.8 dynes/cm2 the number of rolling and firmly adhering leucocytes to mGEnC-1 increased 2-fold after activation with TNF-α, whereas the rolling velocity of the leucocytes decreased 2-fold. Addition of heparin, tinzaparin or HS, and the removal of HS on mGEnC-1 reduced the number of leucocytes rolling and adhering to activated mGEnC-1 about 2–3-fold, while the rolling velocity increased more than 2-fold. Conclusions. HS on activated glomerular endothelial cells is important for the interaction with leucocytes under flow conditions, while exogenous heparinoids interfere with this interaction. These results suggest that supplementary treatment of proliferative glomerulonephritides with heparinoids is an interesting option to pursue.