Spherical Sulfated Cellulose Adsorbs High-Mobility-Group Box Chromosomal Protein 1 In Vitro and In Vivo
Spherical Sulfated Cellulose Adsorbs High-Mobility-Group Box Chromosomal Protein 1 In Vitro and In Vivo
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DOI：
10.1097/mat.0b013e3181d68fa4
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发表时间：
2010-05-01
期刊：
影响因子：
4.2
通讯作者：
Kitagawa, Yuko
中科院分区：
文献类型：
--
作者：
Suda, Koichi;Takeuchi, Hiroya;Kitagawa, Yuko
高迁移率族盒染色体蛋白1(HMGB1)最近被认为是各种急、慢性炎症的晚期介质。一种有效地从体循环中清除HMGB1的方法可能成为治疗HMGB1介导的炎症性疾病的一种有前途的方法。众所周知，HMGB1的阳离子部分与肝素结合，肝素的结构中含有丰富的硫酸盐。在这项研究中，我们确定了球形硫酸纤维素(SC)在体外是否有效地吸附HMGB1以及其他炎症介质。然后，我们在体内研究了SC(SC组)或纤维素珠(对照组)血液灌流对包括HMGB1在内的内源性介质的吸附效果。我们已经证明，与纤维素珠相比，SC在体外对HMGB1、IL-4和IL-8的吸附显著增加。在体内，从开腹和闭合手术后2小时开始，SC血液灌流30分钟，显著降低血清HMGB1水平(p=0.004)，并持续升高血清IL-10水平。这些数据提示使用SC进行血液灌流在治疗HMGB1介导性炎症性疾病中的潜在益处。ASAIO Journal 2010；56：210-214。
High-mobility-group box chromosomal protein 1 (HMGB1) has recently been identified as a late mediator of various kinds of acute and chronic inflammation. A method for efficiently removing HMGB1 from systemic circulation could be a promising therapy for HMGB1-mediated inflammatory diseases. It is well known that the cationic portion of HMGB1 binds to heparin, which has abundant sulfates in its structure. In this study, we determined whether spherical sulfated cellulose (SC) efficiently adsorbed HMGB1, as well as other inflammatory mediators, in vitro. Then, we investigated the efficacy of hemoperfusion with the SC (SC group) or cellulose beads (control group) at adsorbing endogenous mediators, including HMGB1, in vivo. We have demonstrated that the SC adsorbed significantly larger amounts of HMGB1, interleukin (IL)-4, and IL-8 when compared with cellulose beads, in vitro. Hemoperfusion with the SC for 30 minute, starting 2 hour after an abdominal opening and closure operation, significantly reduced serum HMGB1 levels (p = 0.004) and consistently increased serum IL-10 levels, in vivo. These data suggest the potential benefits of hemoperfusion using the SC in treating HMGB1-mediated inflammatory diseases. ASAIO Journal 2010; 56:210-214.