Rousselot Morgane, Delpy Eric, Drieu La Rochelle Christophe, Lagente Vincent, Pirow Ralph, Rees Jean-François, Hagege Agnès, Le Guen Dominique, Hourdez Stéphane, Zal Franck
Equipe Ecophysiologie: Adaptation et Evolution Moléculaires, UPMC - CNRS UMR 7144, Station Biologique, Roscoff, France.
Biotechnol J. 2006 Mar;1(3):333-45. doi: 10.1002/biot.200500049.
The need to develop a blood substitute is now urgent because of the increasing concern over Europe's BSE outbreak and the worldwide HIV/AIDS epidemic, which have cut blood supplies. Extracellular soluble hemoglobin has long been studied for its possible use as a safe and effective alternative to blood transfusion, but this has met with little success. Clinical trials have revealed undesirable side effects-oxidative damage and vasoconstriction-that hamper the application of cell-free hemoglobin as a blood substitute. We have addressed these problems and have found a new promising extracellular blood substitute: the natural giant extracellular polymeric hemoglobin of the polychaete annelid Arenicola marina. Here we show that it is less likely to cause immunogenic response; its functional and structural properties should prevent the side effects often associated with the administration of extracellular hemoglobin. Moreover, its intrinsic properties are of interest for other therapeutic applications often associated with hemorrhagic shock (ischemia reperfusion, treatment of septic shock and for organ preservation prior to transplantation). Moreover, using natural hemoglobin is particularly useful since recombinant DNA techniques could be used to express the protein in large quantities.
由于欧洲疯牛病疫情的日益严重以及全球范围内的艾滋病毒/艾滋病流行，导致血液供应减少，开发血液替代品的需求现在变得紧迫起来。细胞外可溶性血红蛋白长期以来一直被研究，看其是否有可能作为安全有效的输血替代品使用，但这方面进展甚微。临床试验揭示了不良副作用——氧化损伤和血管收缩——这阻碍了无细胞血红蛋白作为血液替代品的应用。我们已经解决了这些问题，并发现了一种新的、有前景的细胞外血液替代品：多毛纲环节动物海蚯蚓的天然巨型细胞外聚合血红蛋白。在这里我们表明，它引发免疫原性反应的可能性较小；其功能和结构特性应能防止通常与细胞外血红蛋白给药相关的副作用。此外，其内在特性对于其他通常与失血性休克（缺血再灌注、脓毒性休克治疗以及移植前器官保存）相关的治疗应用也很有意义。此外，使用天然血红蛋白特别有用，因为可以利用重组DNA技术大量表达这种蛋白质。
