Platelet‐activating factor secreted by DDAVP‐treated monocytes mediates von willebrand factor release from endothelial cells

Abstract

We have previously shown that although DDAVP (1-deamino-8-D-arginine vasopressin), a synthetic analogue of the natural hormone arginine vasopressin, does not directly promote release of vWf from human umbilical vein endothelial cells (ECs), enhanced release does occur when ECs were exposed to either monocytes or to supernatants recovered from DDAVP-treated monocytes. In the present study, we have found that exposure of monocytes to DDAVP did not increase secretion of interleukins (IL)-1 beta, IL-6, IL-8, tumor necrosis factor (TNF-alpha), growth factors G-CSF (granulocyte-), GM-CSF (granulocyte, monocyte-colony stimulating factor), prostaglandins (PG) E2, PGF2 alpha, or PGI2 or purine nucleotides such as ATP and ADP. However, increased levels of platelet-activating factor (PAF) were secreted by DDAVP-treated monocytes in a time- and dose-dependent manner that positively correlated with the enhancement in vWf release from ECs. Moreover, this effect could also be elicited when lipid extracts of these supernatants or purified PAF were added directly to ECs. This response could be inhibited with (+/-)-trans-2,5-Bis(3,4,5-trimethoxyphenyl)-1,3-dioxolane, a specific PAF receptor antagonist, when the ECs were exposed to supernatants from DDAVP-treated monocytes or to pure PAF. The present data indicate that enhanced secretion of PAF from monocytes is one mechanism whereby DDAVP can provoke release of vWf from ECs.

Vasopressin-induced von Willebrand factor secretion from endothelial cells involves V2 receptors and cAMP

“…Several authors have proposed an indirect mechanism for DDAVP-induced vWF secretion: DDAVP activates an intermediate cell, which in turn secretes a vWF-releasing hormone that acts on ECs (6,16). Our data make this hypothesis less attractive, although the existence of two parallel mechanisms cannot be excluded.…”

Effects of desmopressin on platelet membrane glycoproteins and platelet aggregation in volunteers on clopidogrel

“…Its effect seems to be mediated by an indirect mechanism [4] -via the endothelial cell. This mechanism involves the release of factor VIII and von Willebrand factor (vWF) from intracellular protein storage granules [5].…”

Emergency Department Care for Patients with Hemophilia and Von Willebrand Disease

“…Although there are numerous types and subtypes of VWD (Table 4), treatment decisions for bleeding symptoms largely depend on baseline levels of functional VWF and FVIII, and an individual's responsiveness to DDAVP therapy (Table 4). DDAVP, a synthetic vasopressin analogue available for intravenous, subcutaneous, and intranasal administration, stimulates the release of VWF from endothelial cells to raise circulating concentrations of VWF and FVIII (13). For patients with milder forms of VWD (patients with baseline levels of VWF and FVIII Ͼ 10 -20%), DDAVP is usually the treatment of choice for mild or moderate bleeding because hemostatic plasma levels of FVIII and VWF can usually be achieved.…”