title: DDAVP-induced release of von Willebrand factor from endothelial cells in vitro: the effect of plasma and blood cells.
abstract: The vasopressin analogue 1-deamino-8-D-arginine vasopressin (DDAVP) causes an immediate, transient rise in plasma levels of von Willebrand factor (vWF) after its administration. Although it is recognized that vascular endothelial cells play an essential role in this process, the molecular basis of the response is not understood. We have investigated the phenomenon using human umbilical vein endothelial cells as an in vitro model. When normal individuals were stimulated with DDAVP, plasma from blood samples collected subsequently caused the release of vWF from cultured endothelial cells over a 24 h period (22-46% increase over baseline), compared to control plasma (5-17%). DDAVP added directly to the endothelial cells produced no increase in vWF release. When whole blood was treated in vitro with DDAVP, and the plasma subsequently added to endothelial cells, a significant increase in vWF secretion was found. Peripheral blood mononuclear cells were then tested. In the presence of DDAVP, an increased response occurred. Further fractionation of these cells showed that monocytes were largely responsible, causing an increased vWF release of 162% at 2 h. These observations were reinforced by finding that the supernatants of monocytes incubated with DDAVP were also effective in causing increased vWF release (118% compared to 58% for the control sample). Our studies suggest that DDAVP plays an indirect role in causing the release of vWF from endothelial cells, and that peripheral blood monocytes may act as intermediary target cells, which then produce factor(s) acting directly on endothelial cells.
authors.affiliation: Ottawa Centre of the Canadian Red Cross Blood Services.
authors.forename: S
authors.initials: S
authors.lastname: Hashemi
authors.forename: E S
authors.initials: ES
authors.lastname: Tackaberry
authors.forename: D S
authors.initials: DS
authors.lastname: Palmer
authors.forename: G
authors.initials: G
authors.lastname: Rock
authors.forename: P R
authors.initials: PR
authors.lastname: Ganz
mesh_terms: D002478:Cells, Cultured; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D007378:Interleukins; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D014841:von Willebrand Factor; D007371:Interferon-gamma; D013917:Thrombin; D003894:Deamino Arginine Vasopressin; D013755:Tetradecanoylphorbol Acetate