Department of Medical Parasitology and Mycology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Autophagy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Ann Parasitol. 2022;68(3):569-585. doi: 10.17420/ap6803.464.
Leishmaniosis encompasses a group of diseases that is transmitted by sand flies and caused by different species of Leishmania. The skin is the initial organ to be infected by the Leishmania in cutaneous, mucocutaneous and visceral forms of leishmaniosis. The matrix metalloproteinases (MMPs) are capable of degrading all kinds of extracellular matrix (ECM) proteins. The aim of this study was to investigate the protease activity through zymography in cell extracts and extracellular secretions of L. major, L. tropica and L. infantum as three prevalent Leishmania spp. in Iran. The three Leishmania spp. were cultured in RPMI-1640 medium supplemented with fetal calf serum. Promastigotes and axenic amastigotes were harvested and lysed at various phases, and extracellular secretions and cell extracts were collected. Leishmania spp. were proved by targeting kDNA gene. Enzymes were characterized according to gelatin zymography and sensitivity to distinct proteinase inhibitors. We observed proteinase bands with molecular weights (MWs) between 66 to 180 kDa in cellular extracts of axenic amastigotes of L. infantum, L. tropica, and L. major, and from 66 to 92 kDa in extracellular secretions of L. infantum. No proteinase activities were observed in extracellular secretions of axenic amastigotes and in cellular extracts of promastigotes in logarithmic and stationary phases of L. major and L. tropica. Using specific inhibitors, we determined that these proteolytic activities are due to metalloproteases. Our study demonstrated that amastigotes of all three Leishmania spp. have distinct amounts of proteinase activities and therefore can cause various types of lesions and outcomes of the disease.
利什曼病包括一组由沙蝇传播并由不同种利什曼原虫引起的疾病。皮肤是利什曼原虫在皮肤利什曼病、黏膜皮肤利什曼病和内脏利什曼病中感染的初始器官。基质金属蛋白酶(MMPs)能够降解各种细胞外基质(ECM)蛋白。本研究旨在通过同工酶电泳法研究伊朗三种流行的利什曼原虫(L. major、L. tropica 和 L. infantum)的细胞提取物和细胞外分泌物中的蛋白酶活性。将三种利什曼原虫在添加胎牛血清的 RPMI-1640 培养基中培养。在不同阶段收获和裂解前鞭毛体和无鞭毛体阿米巴原虫,并收集细胞外分泌物和细胞提取物。通过靶向 kDNA 基因证实利什曼原虫。根据明胶酶谱法和对不同蛋白酶抑制剂的敏感性来表征酶。我们观察到在无鞭毛体阿米巴原虫的细胞提取物和 L. infantum 的细胞外分泌物中存在分子量(MW)为 66 至 180 kDa 的蛋白酶带,而在 L. infantum 的细胞外分泌物中存在分子量为 66 至 92 kDa 的蛋白酶带。在对数期和静止期的 L. major 和 L. tropica 的前鞭毛体的细胞外分泌物和无鞭毛体的细胞提取物中未观察到蛋白酶活性。使用特异性抑制剂,我们确定这些蛋白水解活性归因于金属蛋白酶。我们的研究表明,所有三种利什曼原虫的无鞭毛体都具有不同数量的蛋白酶活性,因此可以引起各种类型的病变和疾病结果。