MORPHOLOGICAL RELATIONSHIPS OF VONWILLEBRAND-FACTOR, TYPE-VI COLLAGEN, AND FIBRILLIN IN HUMAN VASCULAR SUBENDOTHELIUM

von Willebrand factor (vWF) plays an important role in the process of platelet adhesion after endothelial injury by serving as a bridge betw een constituents of the vascular subendothelium and platelet membrane receptors. We previously presented evidence that type VI collagen micr ofibrils serve as a binding site for vWF in human vascular subendothel ium. However, others have proposed that vWF is not associated with typ e VI collagen but rather with the thicker elastin-associated microfibr ils, which contain several proteins including fibrillin. We therefore investigated the relationships among vWF, type VI collagen, and fibril lin in human vascular subendothelium by immunoelectron microscopy usin g single- and double-labeling immunogold localization techniques. In a ddition, we observed the three-dimensional ultrastructure of vWF-micro fibril complexes by stereo paired micrographs and stereo viewer. We fo und that vWF co-localizes only with the type VI collagen microfibrils in subendothelium but not with fibrillin microfibrils or striated coll agen. The vWF is present in subendothelium in the form of electron-den se aggregates having diameters varying between 65 and 80 nm that are c losely associated with, and en-mesh, the type VI collagen microfibrils and have structural similarities to intracellular Weibel-Palade bodie s. The occasional co-localization of type VI collagen and fibrillin ad jacent to internal elastic lamina was observed. These results are cons istent with the hypothesis that type VI collagen, but not fibrillin-co ntaining microfibrils, serves as a physiologically relevant binding si te for vWF in the vascular subendothelium, where the type VI collagen- vWF complex may play an important role in modulating the hemostatic re sponse to vascular injury.