Matrix metalloproteinases and their tissue inhibitors (TIMPs) in Plasmodium falciparum malaria:: Serum levels of TIMP-1 are associated with disease severity
Matrix metalloproteinases and their tissue inhibitors (TIMPs) in Plasmodium falciparum malaria:: Serum levels of TIMP-1 are associated with disease severity
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DOI：
10.1086/587943
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发表时间：
2008-06-01
影响因子：
6.4
通讯作者：
Kremsner, Peter G.
中科院分区：
文献类型：
--
作者：
Dietmann, Anelia;Helbok, Raimund;Kremsner, Peter G.
背景。恶性疟原虫引起的严重疟疾发病机制的分子机制尚不完全清楚。基质金属蛋白酶（MMP）是通过蛋白水解降解细胞外基质和非基质物质的酶，在调节免疫反应中具有多种功能。 MMP 的主要抑制剂是金属蛋白酶组织抑制剂 (TIMP)。方法。我们使用酶联免疫吸附测定法研究了 50 名加蓬重症疟疾儿童、43 名无并发症疟疾儿童和 27 名健康对照儿童的血清标本中 MMP-8、MMP-9、TIMP-1 和 TIMP-2 的水平。结果。与对照组相比，重症疟疾组和无并发症疟疾组的血清 MMP-8 和 TIMP-1 水平显着升高（P < .001）。与无并发症的疟疾患者相比，重症疟疾患者的 TIMP-1 水平显着升高 (P < .001)。高 TIMP-1 水平与疟疾严重程度显着相关，根据简化的多器官功能障碍评分确定（Spearman 等级相关系数，0.55；P < .001）。结论。 TIMP-1 与严重疟疾的体征和症状有关。严重或无并发症的恶性疟原虫疟疾患者的 MMP-8 水平升高。 MMP 和 TIMP 可能与严重疟疾的发病机制有关，它们要么作为降解细胞外基质的蛋白水解酶，要么作为免疫反应的效应器和调节器。
Background. Molecular mechanisms involved in the pathogenesis of severe malaria caused by Plasmodium falciparum are not fully understood. Matrix metalloproteinases (MMPs) are enzymes that proteolytically degrade both the extracellular matrix and nonmatrix substances with various functions in the modulation of immune response. The key inhibitors of MMPs are the tissue inhibitors of metalloproteinases (TIMPs).Methods. We studied levels of MMP-8, MMP-9, TIMP-1, and TIMP-2 on admission and after 24 h, using an enzyme-linked immunosorbent assay, in serum specimens from 50 Gabonese children with severe malaria, 43 children with uncomplicated malaria, and 27 healthy control children.Results. Serum MMP-8 and TIMP-1 levels were significantly higher in the severe malaria and uncomplicated malaria groups, compared with those in the control group (P < .001). TIMP-1 levels were significantly higher in patients with severe malaria, compared with those in patients with uncomplicated malaria (P < .001). High TIMP-1 levels were significantly correlated with malaria severity, as determined by the simplified multiorgan dysfunction score (Spearman rank-correlation coefficient, 0.55; P < .001).Conclusions. TIMP-1 is associated with signs and symptoms of severe malaria. MMP-8 levels are elevated in patients with severe or uncomplicated P. falciparum malaria. MMPs and TIMPs may be relevant in the pathogenesis of severe malaria, either as proteolytic enzymes that degrade the extracellular matrix or as effectors and regulators of the immune response.