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Platelet-activating factor secreted by DDAVP-treated monocytes mediates von Willebrand factor release from
S Hashemi1, D S Palmer, M T Aye
1Ottawa Centre, Canadian Red Cross, Blood Transfusion Service, Ontario, Canada.
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.
Insights
1-deamino-8-D-arginine vasopressin (DDAVP) stimulates monocytes to release platelet-activating factor (PAF). This PAF then triggers the release of von Willebrand factor (vWf) from endothelial cells.
Area of Science:
- Endocrinology
- Immunology
- Hematology
Background:
- 1-deamino-8-D-arginine vasopressin (DDAVP), a vasopressin analogue, does not directly induce von Willebrand factor (vWf) release from endothelial cells (ECs).
- Previous studies indicated that DDAVP-induced vWf release from ECs is mediated by monocytes.
Purpose of the Study:
- To investigate the specific mechanism by which DDAVP-treated monocytes enhance vWf release from ECs.
- To determine if DDAVP affects the secretion of various inflammatory mediators and nucleotides by monocytes.
Main Methods:
- Monocytes were exposed to DDAVP, and the supernatant was analyzed for various cytokines, growth factors, prostaglandins, and purine nucleotides.
- The effect of DDAVP-treated monocyte supernatants, lipid extracts, and purified platelet-activating factor (PAF) on vWf release from ECs was assessed.
- A specific PAF receptor antagonist was used to block the response in ECs.
Main Results:
- DDAVP exposure did not increase the secretion of interleukins, TNF-alpha, G-CSF, GM-CSF, prostaglandins, or purine nucleotides from monocytes.
- Increased levels of PAF were secreted by DDAVP-treated monocytes in a dose- and time-dependent manner.
- The enhanced vWf release from ECs correlated with increased PAF secretion and could be replicated by adding purified PAF or lipid extracts.
Conclusions:
- Enhanced secretion of platelet-activating factor (PAF) from monocytes is a key mechanism by which DDAVP provokes von Willebrand factor (vWf) release from endothelial cells.
- This finding elucidates a specific cellular pathway involved in DDAVP-mediated hemostatic effects.