The septic milieu triggers expression of spliced tissue factor mRNA in human platelets.
The septic milieu triggers expression of spliced tissue factor mRNA in human platelets.
复制标题
DOI：
10.1111/j.1538-7836.2011.04208.x
复制
发表时间：
2011-04
期刊：
影响因子：
--
通讯作者：
Zimmerman GA
中科院分区：
文献类型：
--
作者：
Rondina MT;Schwertz H;Harris ES;Kraemer BF;Campbell RA;Mackman N;Grissom CK;Weyrich AS;Zimmerman GA
活化的血小板具有先前未被认识的转录后基因表达机制，可能影响止血和炎症。一种新的途径是将静息血小板中的前mrna剪接为成熟的可翻译mrna，以响应细胞活化。我们询问在脓毒症环境中存在的细菌产物和宿主激动剂是否会诱导健康受试者血小板中的组织因子前mrna剪接。同时，我们询问剪接组织因子mRNA是否存在于脓毒症患者的血小板中。组织因子前mRNA和mRNA表达模式在脓毒症患者的血小板和健康受试者的血小板中被细菌、毒素和炎症激动剂激活。还测量了促凝剂活性。健康受试者血小板中活菌、葡萄球菌α-毒素和脂多糖诱导的组织因子前mrna剪接毒素刺激的血小板加速血浆凝血，这一反应被先前描述的剪接抑制剂和抗组织因子抗体阻断。脓毒症患者的血小板表达剪接组织因子mRNA，而在未选择和年龄匹配的对照组中则不存在。组织因子依赖性促凝活性在脓毒症患者的血小板中升高。因此，细菌和宿主因子诱导人血小板中组织因子前mRNA的剪接、组织因子mRNA的表达和组织因子依赖的凝血活性。组织因子mRNA存在于一些脓毒症患者的血小板中，这表明它可能是脓毒症患者血小板表型和功能改变的标志，并且在该综合征中诱导了剪接途径。
Activated platelets have previously-unrecognized mechanisms of post-transcriptional gene expression that may influence hemostasis and inflammation. A novel pathway involves splicing of pre-mRNAs in resting platelets to mature, translatable mRNAs in response to cellular activation. We asked if bacterial products and host agonists present in the septic milieu induce tissue factor pre-mRNA splicing in platelets from healthy subjects. In parallel, we asked if spliced tissue factor mRNA is present in platelets from septic patients in a proof-of-principle analysis. Tissue factor pre-mRNA and mRNA expression patterns were characterized in platelets from septic patients and in platelets isolated from healthy subjects activated with bacteria, toxins, and inflammatory agonists. Procoagulant activity was also measured. Live bacteria, staphylococcal α-toxin, and lipopolysaccharide induced tissue factor pre-mRNA splicing in platelets isolated from healthy subjects. Toxin-stimulated platelets accelerated plasma clotting, a response that was blocked by a previously-characterized splicing inhibitor and by an anti-tissue factor antibody. Platelets from septic patients expressed spliced tissue factor mRNA, whereas it was absent from unselected and age-matched control subjects. Tissue factor-dependent procoagulant activity was elevated in platelets from a subset of septic patients. Thus, bacterial and host factors induce splicing of tissue factor pre-mRNA, expression of tissue factor mRNA, and tissue factor-dependent clotting activity in human platelets. Tissue factor mRNA is present in platelets from some septic patients, indicating that it may be a marker of altered platelet phenotype and function in sepsis and that splicing pathways are induced in this syndrome.
登录
查看更多内容
DOI：
10.1164/rccm.200807-1085oc
发表时间：
2009-03-15
影响因子：
24.7
作者：
Freishtat, Robert J.;Natale, JoAnne;Hoffman, Eric P.
通讯作者：
Hoffman, Eric P.
影响因子：
37.8
作者：
Freedman, JE
通讯作者：
Freedman, JE
影响因子：
8.8
作者：
Levy, MM;Fink, MP;Ramsay, G
通讯作者：
Ramsay, G
影响因子：
64.5
作者：
Denis, MM;Tolley, ND;Weyrich, AS
通讯作者：
Weyrich, AS
影响因子：
6.5
作者：
Cognasse, Fabrice;Hamzeh-Cognasse, Hind;Garraud, Olivier
通讯作者：
Garraud, Olivier