Laboratory of Immunobiology, Rega Institute for Medical Research, University of Leuven, Leuven, Minderbroedersstraat 10, B3000 Leuven, Belgium.
Pharmacol Ther. 2012 Mar;133(3):257-79. doi: 10.1016/j.pharmthera.2011.11.008. Epub 2011 Nov 28.
Matrix metalloproteinases (MMPs) are associated with processes of tissue remodeling and are expressed in all infections with protozoan parasites. We here report the status of MMP research in malaria, trypanosomiasis, leishmaniasis and toxoplasmosis. In all these infections, the balances between MMPs and endogenous MMP inhibitors are disturbed, mostly in favor of active proteolysis. When the infection is associated with leukocyte influx into specific organs, immunopathology and collateral tissue damage may occur. These pathologies include cerebral malaria, sleeping sickness (human African trypanosomiasis), Chagas disease (human American trypanosomiasis), leishmaniasis and toxoplasmic encephalitis in immunocompromised hosts. Destruction of the integrity of the blood-brain barrier (BBB) is a common denominator that may be executed by leukocytic MMPs under the control of host cytokines and chemokines as well as influenced by parasite products. Mechanisms by which parasite-derived products alter host expression of MMP and endogenous MMP inhibitors, have only been described for hemozoin (Hz) in malaria. Hence, understanding these interactions in other parasitic infections remains an important challenge. Furthermore, the involved parasites are also known to produce their own metalloproteinases, and this forms an extra stimulus to investigate MMP inhibitory drugs as therapeutics. MMP inhibitors (MMPIs) may dampen collateral tissue damage, as is anecdotically reported for tetracyclines as MMP regulators in parasite infections.
基质金属蛋白酶（MMPs）与组织重塑过程有关，存在于所有原生动物寄生虫感染中。我们在此报告疟疾、锥虫病、利什曼病和弓形体病中 MMP 研究的现状。在所有这些感染中，MMP 与内源性 MMP 抑制剂之间的平衡被打破，大多数情况下有利于活性蛋白水解。当感染与白细胞流入特定器官有关时，可能会发生免疫病理学和继发性组织损伤。这些病理包括脑型疟疾、昏睡病（非洲人类锥虫病）、恰加斯病（美洲人类锥虫病）、利什曼病和免疫功能低下宿主的弓形体脑炎。破坏血脑屏障（BBB）的完整性是一个共同点，白细胞 MMP 可能在宿主细胞因子和趋化因子的控制下以及寄生虫产物的影响下执行。寄生虫产物改变宿主 MMP 和内源性 MMP 抑制剂表达的机制，仅在疟疾中的血影蛋白（Hz）中有所描述。因此，了解其他寄生虫感染中的这些相互作用仍然是一个重要的挑战。此外，已知涉及的寄生虫也会产生自己的金属蛋白酶，这形成了一个额外的刺激因素，以研究 MMP 抑制药物作为治疗方法。MMP 抑制剂（MMPI）可能会减轻继发性组织损伤，正如在寄生虫感染中四环素有 MMP 调节剂的情况一样。
