Balancing role of nitric oxide in complement-mediated activation of platelets from mCd59a and mCd59b double-knockout mice.
Balancing role of nitric oxide in complement-mediated activation of platelets from mCd59a and mCd59b double-knockout mice.
复制标题
DOI：
10.1002/ajh.21363
复制
发表时间：
2009-04
影响因子：
12.8
通讯作者：
Halperin, Jose A.
中科院分区：
文献类型：
--
作者：
Qin, Xuebin;Hu, Weiguo;Song, Wenping;Blair, Price;Wu, Gongxiong;Hu, Xuemei;Song, Yanli;Bauer, Selena;Feelisch, Martin;Leopold, Jane A.;Loscalzo, Joseph;Halperin, Jose A.
CD59是补体膜攻击复合物（MAC）的膜蛋白抑制剂。据报道，mCd59基因敲除小鼠表现出溶血性贫血和血小板活化。这种表型类似于人类溶血性贫血，即阵发性夜间血红蛋白尿（PNH），其中血小板活化和血栓形成起关键的致病作用。长期以来，人们一直怀疑补体和一氧化氮（NO）都有助于PNH血栓形成，但尚未正式证明。利用mCd59a和mCd59b双敲除小鼠（mCd59ab−/−小鼠）在补体充足（C3+/+）和补体缺乏（C3−/−）的背景下，我们发现mCd59ab−/−血小板对补体介导的激活敏感，并为mCd59ab−/−小鼠体内血小板激活提供了可能的证据。使用L-NAME （NO-合成酶抑制剂）和NOC-18或SNAP （NO-供体）的组合，我们进一步证明NO调节补体介导的血小板活化。这些结果表明，PNH患者的血栓形成能力可能是由于补体介导的血小板活化增加和溶血导致的no生物利用度降低的结合。
CD59 is a membrane protein inhibitor of the membrane attack complex (MAC) of complement. mCd59 knockout mice reportedly exhibit hemolytic anemia and platelet activation. This phenotype is comparable to the human hemolytic anemia known as paroxysmal nocturnal hemoglobinuria (PNH), in which platelet activation and thrombosis play a critical pathogenic role. It has long been suspected but not formally demonstrated that both complement and nitric oxide (NO) contribute to PNH thrombosis. Using mCd59a and mCd59b double knockout mice (mCd59ab−/− mice) in complement sufficient (C3+/+) and deficient (C3−/−) backgrounds, we document that mCd59ab−/− platelets are sensitive to complement-mediated activation and provide evidence for possible in vivo platelet activation in mCd59ab−/− mice. Using a combination of L-NAME (a NO-synthase inhibitor) and NOC-18 or SNAP (NO-donors), we further demonstrate that NO regulates complement-mediated activation of platelets. These results indicate that the thrombotic diathesis of PNH patients could be due to a combination of increased complement-mediated platelet activation and reduced NO-bioavailability as a consequence of hemolysis.
登录
查看更多内容
影响因子：
4.2
作者：
Bellander, BM;Singhrao, SK;Svensson, M
通讯作者：
Svensson, M
影响因子：
7.7
作者：
Qin, XB;Goldfine, A;Halperin, JA
通讯作者：
Halperin, JA
DOI：
10.1007/s00464-004-8213-6
发表时间：
2005-08-01
影响因子：
3.1
作者：
Lee, EC;Rafiq, A;Dennerlein, JT
通讯作者：
Dennerlein, JT
影响因子：
12.8
作者：
Qin, Xuebin;Hu, Weiguo;Song, Wenping;Grubissich, Luciano;Hu, Xuemei;Wu, Gongxiong;Ferris, Sean;Dobarro, Martin;Halperin, Jose A.
通讯作者：
Halperin, Jose A.
影响因子：
20.3
作者：
Kleinbongard, P;Schulz, R;Kelm, M
通讯作者：
Kelm, M