Heparan sulfate in glomerular inflammation.

The number of patients with glomerulonephritis worldwide is approximately 1.5 million and is still increasing. Proliferative glomerulonephritis is manifested in a range of diseases, such as anti-glomerular basement membrane (GBM) glomerulonephritis, lupus glomerulonephritis, IgA nephropathy, mesangial proliferative glomerulonephritis and ANCA-asoociated vasculitis. Proliferative glomerulonephritis is characterized by the influx of inflammatory cells (leukocytes) and it has been demonstrated that heparan sulfate (HS) is important during inflammation. Treatment of glomerulonephritis consists of immunosuppressive drugs like corticosteroids and cyclophosphamide, which takes several days before their effects become evident. Since therapeutic intervention with heparinoids prevents leukocyte adhesion/influx and disease manifestation in inflamed tissue, heparin/heparinoids are also clinically applied. However,the main application of heparin/heparinoids still is its use as anticoagulant. It can be more safely used as an anti-inflammatory drug, if the anticoagulant properties are abrogated, leaving the anti-inflammatory properties unchanged.For the rational development of new synthetic and defined heparinoids that could be used as a more specific intervention therapy in patients with glomerulonephritis, it is crucial to identify which glomerular endothelial HS structures are responsible for leukocyte binding during glomerulonephritis. In this thesis, the expression of specific HS structures by glomerular endothelial cells and their role in leukocyte adhesion was studied in vitro and in various models of glomerulonephritis in vivo