Platelet-activating factor secreted by DDAVP-treated monocytes mediates von Willebrand factor release from endothelial cells.
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.
Hashemi
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S
Ottawa Centre, Canadian Red Cross, Blood Transfusion Service, Ontario, Canada.
Palmer
D S
DS
Aye
M T
MT
Ganz
P R
PR
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology*; D004148:Dioxolanes / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D010972:Platelet Activating Factor / Q000378:metabolism* / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism*
C067891:2,5-bis(3,4,5-trimethoxyphenyl)-1,3-dioxolane; D016207:Cytokines; D004148:Dioxolanes; D010972:Platelet Activating Factor; D011453:Prostaglandins; D014841:von Willebrand Factor; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D011464:Epoprostenol; D003894:Deamino Arginine Vasopressin