Transgenic sickle mice have vascular inflammation
Transgenic sickle mice have vascular inflammation
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DOI：
10.1182/blood-2002-10-3313
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发表时间：
2003-05-15
期刊：
影响因子：
20.3
通讯作者：
Vercellotti, GM
中科院分区：
文献类型：
--
作者：
Belcher, JD;Bryant, CJ;Vercellotti, GM
炎症可能在镰状细胞病的血管闭塞中起重要作用。镰状血球患者白细胞计数高，血清g反应蛋白（CRP）、细胞因子和粘附分子水平升高。此外，循环中的内皮细胞、白细胞和血小板也被激活。我们检测了4只表达人类α -和镰状β -珠蛋白基因的转基因小鼠模型，以确定它们是否模拟了患者的炎症反应。这些小鼠模型被命名为NY-S、Berk-S- antilles、NY-S /S-Antilles （NY-S X Berk-S- antilles）和Berk-S。平均白细胞计数升高1.4 ~ 2.1倍(P <或等于。01)在Berk-S- antilles， Ny-S/S-Antiller和Berk-S小鼠中，但在Ny-S小鼠中与对照组相比没有。血清淀粉P组分（SAP）是一种急性期反应蛋白，与CRP序列同源性为60% ~ 70%，升高8.5 ~ 12.1倍（P小于或等于CRP）。001)在转基因镰状小鼠中。血清白细胞介素-6 （IL-6）升高1.6 ~ 1.9倍（P < = 0.05）。Western blots证实免疫组化染色，血管细胞黏附分子（VCAM）、细胞间黏附分子（ICAM）、血小板内皮细胞黏附分子（PECAM）均上调3 ~ 54old （P <或等于P < 0.05）。05)在镰状小鼠的肺中。核糖核酸酶保护实验（RPAs）显示，镰状小鼠的VCAM mRNA也升高了1.2- 1.4倍（P小于或等于0.01）。核因子kappaB （NF-kappaB）是炎症反应的关键转录因子，升高1.9倍(P小于或等于。006)在NY-S镰状小鼠肺中。我们得出结论，转基因镰状小鼠是研究血管炎症和抗炎治疗预防镰状细胞病血管闭塞的潜在益处的良好模型。(C) 2003年由美国血液病学会出版。
Inflammation may play an essential role in vaso-occlusion in sickle cell disease. Sickle patients have high white counts and elevated levels of serum G-reactive protein (CRP), cytokines, and adhesion molecules. In addition, circulating endothelial cells, leukocytes, and platelets are activated. We examined 4 transgenic mouse models expressing human alpha- and sickle beta-globin genes to determine if they mimic the inflammatory response seen in patients. These mouse models are designated NY-S, Berk-S-Antilles, Ny-S/S-Antilles (NY-S X Berk-S-Antilles), and Berk-S. The mean white counts were elevated 1.4- to 2.1-fold (P less than or equal to .01) in the Berk-S-Antilles, Ny-S/S-Antiller, and Berk-S mice, but not in the NY-S mice compared with controls. Serum amylold P-component (SAP), an acute-phase response protein with 60% to 70% sequence homology to CRP, was elevated 8.5- to 12.1-fold (P less than or equal to .001) in transgenic sickle mice. Similarly, serum interleukin-6 (IL-6) was elevated 1.6- to 1.9-fold (P less than or equal to .05). Western blots, confirming immunohistochemical staining, showed vascular cell adhesion molecule (VCAM), intercellular adhesion molecule (ICAM), and platelet-endothelial cell adhesion molecule (PECAM) were up-regulated 3- to 54old (P less than or equal to .05) in the lungs of sickle mice. Ribo-nuclease protection assays (RPAs) demonstrated VCAM mRNA also was elevated in sickle mice 1.2- to 1.4-fold (P less than or equal to .01). Nuclear factor kappaB (NF-kappaB), a transcription factor critical for the inflammatory response, was elevated 1.9-fold (P less than or equal to .006) in NY-S sickle mouse lungs. We conclude that transgenic sickle mice are good models to study vascular inflammation and the potential benefit of anti-inflammatory therapies to prevent vaso-occlusion in sickle cell disease. (C) 2003 by The American Society of Hematology.