Kettlun Ana M, Cartier Luis, García Lorena, Collados Lucía, Vásquez Felipe, Ramírez Eugenio, Valenzuela M Antonieta
Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Casilla 233 Correo 1, Santiago, Chile.
Life Sci. 2003 May 9;72(25):2863-76. doi: 10.1016/s0024-3205(03)00146-2.
The tropical spastic paraparesis or human T-cell lymphotropic virus associated myelopathy (TSP/HAM), has been related with an overexpression of matrix metalloproteinases (MMPs), especially MMP-9. Initial studies of reverse zymography with cerebrospinal fluid (CSF) from TSP/HAM patients, and controls showed the presence of TIMPs, endogenous MMP inhibitors. We determined in CSF the levels of TIMPs by immunoanalysis in 25 patients with TSP/HAM, and compared with two groups: controls and patients with acute and subacute inflammatory neurological diseases. We found that TIMP-2, TIMP-3 and TIMP-4 levels were significantly higher than in controls in both TSP/HAM and inflammatory patients, while TIMP-1 was increased only in the inflammatory group. Levels of MMP-3 and MMP-9 from the two groups of patients showed a significant upregulation in CSF. In the CSF of around the 70% of TSP-HAM and inflammatory patients the presence MMP-9 was detected by zymography, but not in controls. MMP-2 was only overexpressed in the acute inflammatory group. The active form of MMP-2 was observed in both groups of patients with a similar high frequency (60%). MMPs overexpressions are independent of the evolution time of the disease in TSP/HAM. The chronic overexpression of these extracelullar matrix proteins detected in CSF of TSP/HAM should be indirectly produced by secreted viral proteins being responsible for the progression of this disease, accounting for the observed differences with acute inflammatory patients. Our results support the existence of an imbalance between MMPs and their endogenous tissue inhibitors, which could be a pathogenic factor in the chronicity of TSP/HAM.
热带痉挛性截瘫或人类嗜T细胞病毒相关脊髓病（TSP/HAM）与基质金属蛋白酶（MMPs）的过度表达有关，尤其是MMP-9。对TSP/HAM患者和对照者的脑脊液（CSF）进行反向酶谱分析的初步研究显示，存在内源性MMP抑制剂组织金属蛋白酶抑制剂（TIMPs）。我们通过免疫分析测定了25例TSP/HAM患者脑脊液中TIMPs的水平，并与两组进行比较：对照组以及患有急性和亚急性炎症性神经系统疾病的患者。我们发现，TSP/HAM患者和炎症患者的TIMP-2、TIMP-3和TIMP-4水平均显著高于对照组，而TIMP-1仅在炎症组中升高。两组患者脑脊液中MMP-3和MMP-9的水平均显著上调。在约70%的TSP-HAM患者和炎症患者的脑脊液中，通过酶谱法检测到MMP-9的存在，但对照组中未检测到。MMP-2仅在急性炎症组中过度表达。在两组患者中均观察到MMP-2的活性形式，频率相似（60%）。MMPs的过度表达与TSP/HAM疾病的病程无关。在TSP/HAM患者脑脊液中检测到的这些细胞外基质蛋白的慢性过度表达，可能是由分泌的病毒蛋白间接导致的，这些病毒蛋白是该疾病进展的原因，这也解释了与急性炎症患者观察到的差异。我们的结果支持MMPs与其内源性组织抑制剂之间存在失衡，这可能是TSP/HAM慢性化的致病因素。
