Heme oxygenase-1 is a modulator of inflammation and vaso-occlusion in transgenic sickle mice
Heme oxygenase-1 is a modulator of inflammation and vaso-occlusion in transgenic sickle mice
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DOI：
10.1172/jci26857
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发表时间：
2006-03-01
影响因子：
15.9
通讯作者：
Vercellotti, GM
中科院分区：
文献类型：
--
作者：
Belcher, JD;Mahaseth, H;Vercellotti, GM
表达β（S）血红蛋白的转基因镰状小鼠具有活化的血管内皮。其显示NF-κ B B和粘附分子的表达增强，促进镰状小鼠的血管淤滞，而不是正常小鼠对缺氧/复氧的反应。镰状小鼠体内红细胞溶血，表现为网织红细胞计数、血浆血红蛋白和胆红素增加，血浆结合珠蛋白减少。血红素含量在镰状器官中升高，这促进血管炎症和血红素加氧酶-1表达。用氯化血红素治疗镰状小鼠进一步增加血红素加氧酶-1表达，并抑制缺氧/复氧诱导的停滞、白细胞-内皮相互作用以及NF-κ B、VCAM-1和ICAM-1表达。锡原卟啉抑制血红素加氧酶可加重镰状小鼠的血瘀。此外，用血红素加氧酶产物一氧化碳或胆绿素处理镰状小鼠抑制了停滞和NF-κ B、VCAM-1和ICAM-1表达。血红素加氧酶-1腺病毒皮下给药增加血红素加氧酶-1和抑制缺氧/再氧诱导的皮肤淤滞镰状小鼠。血红素加氧酶- I在抑制转基因镰状小鼠血管闭塞中起重要作用。
Transgenic sickle mice expressing beta(S) hemoglobin have activated vascular endothelium. that exhibits enhanced expression of NF-kappa B and adhesion molecules that promote vascular stasis in sickle, but not in normal, mice in response to hypoxia/reoxygenation. Sickle mice hemolyze rbcs in vivo as demonstrated by increased reticulocyte counts, plasma hemoglobin and bilirubin, and reduced plasma haptoglobin. The heme content is elevated in sickle organs, which promotes vascular inflammation and heme oxygenase-1 expression. Treatment of sickle mice with hemin further increases heme oxygenase-1 expression and inhibits hypoxia/reoxygenation-induced stasis, leukocyte-endothelium interactions, and NF-kappa B, VCAM-1, and ICAM-1 expression. Heme oxygenase inhibition by tin protoporphyrin exacerbates stasis in sickle mice. Furthermore, treatment of sickle mice with the heme oxygenase enzymatic product carbon monoxide or biliverdin inhibits stasis and NF-kappa B, VCAM-1, and ICAM-1 expression. Local administration of heme oxygenase-1 adenovirus to subcutaneous skin increases heme oxygenase-1 and inhibits hypoxia/reoxygenation-induced stasis in the skin of sickle mice. Heme oxygenase- I plays a vital role in the inhibition of vaso-occlusion in transgenic sickle mice.