Hashemi S, Palmer D S, Aye M T, Ganz P R
Ottawa Centre, Canadian Red Cross, Blood Transfusion Service, Ontario, Canada.
J Cell Physiol. 1993 Mar;154(3):496-505. doi: 10.1002/jcp.1041540307.
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.
我们之前已经表明，尽管天然激素精氨酸加压素的合成类似物去氨加压素（1-脱氨基-8-D-精氨酸加压素）不会直接促进人脐静脉内皮细胞（ECs）释放血管性血友病因子（vWf），但当ECs暴露于单核细胞或从去氨加压素处理的单核细胞中回收的上清液时，确实会出现vWf释放增强的情况。在本研究中，我们发现单核细胞暴露于去氨加压素不会增加白细胞介素（IL）-1β、IL-6、IL-8、肿瘤坏死因子（TNF-α）、生长因子粒细胞集落刺激因子（G-CSF）、粒细胞-巨噬细胞集落刺激因子（GM-CSF）、前列腺素（PG）E2、PGF2α或PGI2或嘌呤核苷酸如ATP和ADP的分泌。然而，去氨加压素处理的单核细胞以时间和剂量依赖性方式分泌增加的血小板活化因子（PAF），这与ECs中vWf释放的增强呈正相关。此外，当将这些上清液的脂质提取物或纯化的PAF直接添加到ECs中时，也能引发这种效应。当ECs暴露于去氨加压素处理的单核细胞的上清液或纯PAF时，这种反应可以被特异性PAF受体拮抗剂（±）-反式-2,5-双（3,4,5-三甲氧基苯基）-1,3-二氧戊环抑制。目前的数据表明，单核细胞中PAF分泌的增加是去氨加压素能够激发ECs释放vWf的一种机制。
