von Willebrand factor antigen compared with other factors in vasculitic syndromes.

In order to analyse their role as a specific marker of vascular damage and their value in monitoring disease activity the plasma concentrations of von Willebrand factor antigen (vWFAg) and the ristocetin cofactor (RiCoF) activities were determined in 43 children with vasculitis and 20 controls. These patients were sub-divided into three groups according to diagnosis: Henoch-Schönlein purpura (n = 18), polyarteritis nodosa (n = 16), and systemic lupus erythematosus (n = 9). High concentrations of vWFAg and activities of RiCoF were found in all the patient groups. vWFAg and RiCoF returned to normal as the patients became symptom free and remained above normal in those with continuing symptoms. The amount of vWFAg did not correlate with the acute phase reactants. vWFAg acted as a specific marker of vascular damage and was useful for the monitoring of disease activity both in small vessel vasculitis and systemic necrotising arteritis

Selective and Signal-dependent Recruitment of Membrane Proteins to Secretory Granules Formed by Heterologously Expressed von Willebrand Factor

von Willebrand factor (vWF) is a large, multimeric protein secreted by endothelial cells and involved in hemostasis. When expressed in AtT-20 cells, vWF leads to the de novo formation of cigar-shaped organelles similar in appearance to the Weibel-Palade bodies of endothelial cells in which vWF is normally stored before regulated secretion. The membranes of this vWF-induced organelle, termed the pseudogranule, are uncharacterized. We have examined the ability of these pseudogranules, which we show are secretagogue responsive, to recruit membrane proteins. Coexpression experiments show that the Weibel-Palade body proteins P-selectin and CD63, as well as the secretory organelle membrane proteins vesicle-associated membrane protein-2 and synaptotagmin I are diverted away from the endogenous adrenocorticotropic hormone-containing secretory granules to the vWF-containing pseudogranules. However, transferrin receptor, lysosomal-associated membrane protein 1, and sialyl transferase are not recruited. The recruitment of P-selectin is dependent on a tyrosine-based motif within its cytoplasmic domain. Our data show that vWF pseudogranules specifically recruit a subset of membrane proteins, and that in a process explicitly driven by the pseudogranule content (i.e., vWF), the active recruitment of at least one component of the pseudogranule membrane (i.e., P-selectin) is dependent on residues of P-selectin that are cytosolic and therefore unable to directly interact with vWF