Wei Xiao-Long, Wei Ji-Fu, Li Tao, Qiao Li-Ya, Liu Yue-Lin, Huang Tian, He Shao-Heng
Allergy and Inflammation Research Institute, The Key Immunopharmacology Laboratory of Guangdong Province, Shantou University Medical College, 22 Xin-ling Road, Shantou, Guangdong 515041, China.
Toxicon. 2007 Dec 15;50(8):1126-39. doi: 10.1016/j.toxicon.2007.07.022. Epub 2007 Aug 8.
L-amino acid oxidases (LAOs) are one of the major components of snake venoms, which possess numerous biological functions. However, little is known of the influence of LAOs on organ lesions. In the present study, a unique LAO from Agkistrodon blomhoffii ussurensis snake venom named ABU-LAO was purified by Heparin-Sepharose FF chromatography followed by an ion-exchange chromatography procedure. The purified ABU-LAO appears a dimer with a molecular mass of approximately 108.8kDa. Kinetics studies showed that ABU-LAO is very active towards its substrates L-Asn, L-Phe, L-Tyr, L-Leu, L-Ile and L-Trp. The most striking observation in the present study is that ABU-LAO causes severe pneumorrhagia, pulmonary interstitial edema, fusion of pulmonary alveoli, cardiac interstitial edema and bleeding when being intravenously injected into BALB/c mice. ABU-LAO also induces liver cell necrosis and release of cytokines including IL-6, IL-12 and IL-2 from highly purified human peripheral blood monocytes and T cells, respectively. In conclusion, ABU-LAO potently induces lesions in lungs and livers. The ability of ABU-LAO will contribute to the understanding of the pathogenesis of snakebite wound.
L-氨基酸氧化酶(LAOs)是蛇毒的主要成分之一,具有多种生物学功能。然而,关于LAOs对器官损伤的影响却知之甚少。在本研究中,通过肝素-琼脂糖凝胶FF柱层析,随后进行离子交换层析,从乌苏里蝮蛇蛇毒中纯化出一种独特的LAO,命名为ABU-LAO。纯化后的ABU-LAO呈现为二聚体,分子量约为108.8 kDa。动力学研究表明,ABU-LAO对其底物L-天冬酰胺、L-苯丙氨酸、L-酪氨酸、L-亮氨酸、L-异亮氨酸和L-色氨酸具有很高的活性。本研究中最引人注目的发现是,将ABU-LAO静脉注射到BALB/c小鼠体内时,会导致严重的肺出血、肺间质水肿、肺泡融合、心脏间质水肿和出血。ABU-LAO还分别诱导高度纯化的人外周血单核细胞和T细胞发生肝细胞坏死,并释放细胞因子,包括IL-6、IL-12和IL-2。总之,ABU-LAO能有效诱导肺和肝损伤。ABU-LAO的这种能力将有助于理解蛇咬伤伤口的发病机制。