Yang Junwei, Zhang Yixuan, Xu Jing, Geng Yan, Chen Xiaoying, Yang Hongliang, Wang Shengnian, Wang Hengan, Jiang Xucheng, Guo Xiaokui, Zhao Guoping
Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
PLoS One. 2009;4(1):e4181. doi: 10.1371/journal.pone.0004181. Epub 2009 Jan 15.
Pulmonary hemorrhage has been recognized as a major, often lethal, manifestation of severe leptospirosis albeit the pathogenesis remains unclear. The Leptospira interrogans virulent serogroup Icterohaemorrhagiae serovar Lai encodes a protein (LA2144), which exhibited the platelet-activating factor acetylhydrolase (PAF-AH) activity in vitro similar to that of human serum with respect to its substrate affinity and specificity and thus designated L-PAF-AH. On the other hand, the primary amino acid sequence of L-PAF-AH is homologous to the alpha1-subunit of the bovine brain PAF-AH isoform I. The L-PAF-AH was proven to be an intracellular protein, which was encoded unanimously and expressed similarly in either pathogenic or saprophytic leptospires. Mongolian gerbil is an appropriate experimental model to study the PAF-AH level in serum with its basal activity level comparable to that of human while elevated directly associated with the course of pulmonary hemorrhage during severe leptospirosis. Mortality occurred around the peak of pulmonary hemorrhage, along with the transition of the PAF-AH activity level in serum, from the increasing phase to the final decreasing phase. Limited clinical data indicated that the serum activity of PAF-AH was likely to be elevated in the patients infected by L. interrogans serogroup Icterohaemorrhagiae, but not in those infected by other less severe serogroups. Although L-PAF-AH might be released into the micro-environment via cell lysis, its PAF-AH activity apparently contributed little to this elevation. Therefore, the change of PAF-AH in serum not only may be influential for pulmonary hemorrhage, but also seems suitable for disease monitoring to ensure prompt clinical treatment, which is critical for reducing the mortality of severe leptospirosis.
肺出血一直被认为是严重钩端螺旋体病的一种主要且往往致命的表现，尽管其发病机制尚不清楚。问号钩端螺旋体致病血清群出血性黄疸型赖株编码一种蛋白（LA2144），该蛋白在体外表现出与人类血清相似的血小板活化因子乙酰水解酶（PAF-AH）活性，就其底物亲和力和特异性而言，因此被命名为L-PAF-AH。另一方面，L-PAF-AH的一级氨基酸序列与牛脑PAF-AH同工型I的α1亚基同源。L-PAF-AH被证明是一种细胞内蛋白，在致病性或腐生性钩端螺旋体中均一致编码且表达相似。蒙古沙鼠是研究血清中PAF-AH水平的合适实验模型，其基础活性水平与人类相当，而在严重钩端螺旋体病期间，其活性水平直接与肺出血的进程相关而升高。死亡率发生在肺出血高峰期左右，同时血清中PAF-AH活性水平从上升阶段过渡到最终下降阶段。有限的临床数据表明，感染问号钩端螺旋体出血性黄疸型血清群的患者血清PAF-AH活性可能升高，但感染其他症状较轻血清群的患者则不然。尽管L-PAF-AH可能通过细胞裂解释放到微环境中，但其PAF-AH活性显然对这种升高贡献不大。因此，血清中PAF-AH的变化不仅可能对肺出血有影响，而且似乎适合用于疾病监测以确保及时进行临床治疗，这对于降低严重钩端螺旋体病的死亡率至关重要。
