Serum activity of platelet-activating factor acetylhydrolase is a potential clinical marker for leptospirosis pulmonary hemorrhage.

Serum activity of platelet-activating factor acetylhydrolase is a potential clinical marker for leptospirosis pulmonary hemorrhage.
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血小板激活因子乙酰水解酶的血清活性是钩端螺旋体病肺出血的潜在临床标志物

DOI:
10.1371/journal.pone.0004181
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发表时间:
2009
期刊:
影响因子:
3.7
通讯作者:
Zhao G
Zhao G
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Yang J;Zhang Y;Xu J;Geng Y;Chen X;Yang H;Wang S;Wang H;Jiang X;Guo X;Zhao G

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肺出血已被认为是一个主要的,往往是致命的,表现严重钩端螺旋体病,虽然发病机制仍不清楚。问号钩端螺旋体(Leptospira interrogans)黄疸出血群(Iterohemorrhagiae serovar Lai)编码一种蛋白(LA 2144),该蛋白在体外表现出与人血清相似的血小板活化因子乙酰水解酶(PAF-AH)活性,因此命名为L-PAF-AH。另一方面,L-PAF-AH的一级氨基酸序列与牛脑PAF-AH亚型I的α1-亚基同源。已证实L-PAF-AH是一种胞内蛋白,在致病性钩端螺旋体和嗜血性钩端螺旋体中编码一致,表达相似。长爪沙鼠是研究血清PAF-AH水平的理想动物模型,其基础活性水平与人相当,但其升高与重症钩体病肺出血的病程直接相关。死亡发生在肺出血高峰前后,沿着血清PAF-AH活性由升高期向最终下降期过渡。有限的临床资料提示,L.问号血清群黄疸出血型,但不是在那些感染其他较轻的血清群。虽然L-PAF-AH可能通过细胞裂解释放到微环境中,但其PAF-AH活性对这种升高的贡献很小。因此,血清PAF-AH的变化不仅对肺出血有一定的影响,而且可用于病情监测,以确保及时的临床治疗,这对降低重症钩体病的死亡率至关重要。
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 α1-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.
DOI: 10.1097/00003246-199402000-00009
发表时间: 1994-02-01
影响因子: 8.8
作者:
GRAHAM, RM;STEPHENS, CJ;TAYLOR, RR
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影响因子: 3.1
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