Morphological relationships of von Willebrand 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 between constituents of the vascular subendothelium and platelet membrane receptors. We previously presented evidence that type VI collagen microfibrils serve as a binding site for vWF in human vascular subendothelium. However, others have proposed that vWF is not associated with type VI collagen but rather with the thicker elastin-associated microfibrils, which contain several proteins including fibrillin. We therefore investigated the relationships among vWF, type VI collagen, and fibrillin in human vascular subendothelium by immunoelectron microscopy using single- and double-labeling immunogold localization techniques. In addition, we observed the three-dimensional ultrastructure of vWF-microfibril complexes by stereo paired micrographs and stereo viewer. We found that vWF co-localizes only with the type VI collagen microfibrils in subendothelium but not with fibrillin microfibrils or striated collagen. The vWF is present in subendothelium in the form of electron-dense aggregates having diameters varying between 65 and 80 nm that are closely associated with, and enmesh, the type VI collagen microfibrils and have structural similarities to intracellular Weibel-Palade bodies. The occasional co-localization of type VI collagen and fibrillin adjacent to internal elastic lamina was observed. These results are consistent with the hypothesis that type VI collagen, but not fibrillin-containing microfibrils, serves as a physiologically relevant binding site for vWF in the vascular subendothelium, where the type VI collagen-vWF complex may play an important role modulating the hemostatic response to vascular injury.
Wu
X X
XX
Department of Medicine, The Mount Sinai School of Medicine, New York, New York, USA.
Gordon
R E
RE
Glanville
R W
RW
Kuo
H J
HJ
Uson
R R
RR
Rand
J H
JH
D003094:Collagen / Q000378:metabolism / Q000648:ultrastructure*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000648:ultrastructure*; D016326:Extracellular Matrix Proteins / Q000378:metabolism / Q000648:ultrastructure*; D000071837:Fibrillins; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D008840:Microfilament Proteins / Q000378:metabolism / Q000648:ultrastructure*; D016253:Microscopy, Immunoelectron; D014469:Umbilical Arteries / Q000737:chemistry / Q000648:ultrastructure; D014471:Umbilical Veins / Q000737:chemistry / Q000648:ultrastructure; D014841:von Willebrand Factor / Q000378:metabolism / Q000648:ultrastructure*
D016326:Extracellular Matrix Proteins; D000071837:Fibrillins; D008840:Microfilament Proteins; D014841:von Willebrand Factor; D003094:Collagen