Platelet factor 4 binding to glomerular microvascular matrix.
Platelet factor 4, a unique peptide released during platelet aggregation, can bind to natural sulfated glycosaminoglycans from human renal cortex. The glycosaminoglycan isolate contained components sensitive to hyaluronidase, chondroitinase ABC and nitrous acid. Binding was demonstrated by the change in electrophoretic mobility of platelet factor 4 applied in combination with glycosaminoglycan compared to either applied alone. This effect, which occurred at physiologic pH but not at acidic pH or with high ionic strength, was preserved in samples subjected to prior hyaluronidase and chondroitinase digestion. Further demonstration that platelet factor 4 can interact with heparan sulfate anionic sites in the glomerular microvascular matrix was obtained by incubating radiolabeled platelet factor 4 with isolated rat glomeruli, and with purified human and rat glomerular basement membrane, followed by displacement with heparin. Total binding and heparin-released binding were decreased in glomerular basement membrane prepared from diabetic patients and from rats with streptozotocin-diabetes compared to control samples. These findings implicate platelet factor 4 in the pathogenesis of the altered capillary integrity associated with diabetes, and provide novel evidence that heparan sulfate anionic sites in glomerular basement membrane are diminished in human and experimental diabetes.
D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D002196:Capillaries / Q000378:metabolism; D002417:Cattle; D003920:Diabetes Mellitus / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism*; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D007672:Kidney Cortex / Q000032:analysis*; D007678:Kidney Glomerulus / Q000098:blood supply*; D010978:Platelet Factor 4 / Q000378:metabolism*; D051381:Rats
D006025:Glycosaminoglycans; D006497:Heparan Sulfate; D010978:Platelet Factor 4