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在美洲钩虫和巴西钩虫前鞭毛体中 MMP-2 和 MMP-9 的检测和活性。

Detection and activity of MMP-2 and MMP-9 in Leishmania amazonensis and Leishmania braziliensis promastigotes.

机构信息

Laboratory of Electron Microscopy, Section of Hepatology, Evandro Chagas Institute, Belém, Pará, Brazil.

Department of Oral Pathology, School of Dentistry, Federal University of Para, Belém, Pará, Brazil.

出版信息

BMC Microbiol. 2023 Aug 16;23(1):223. doi: 10.1186/s12866-023-02973-z.

Abstract

Metalloproteinases (MMPs) are remarkable zinc-dependent endopeptidases, critical for degrading components of the extracellular matrix, thus actively influencing cell migration. Their impact on intracellular parasites, such as the enigmatic protozoan Leishmania, elicits intriguing queries. This study explores into the untapped territory of MMP-2 and MMP-9 within Leishmania spp. promastigotes. Notably, we successfully detected and quantified these MMPs, while also evaluating their activity in two distinct Leishmania species-L. amazonensis (La) and L. braziliensis (Lb)-at various growth stages and isolated from distinct clinical tegumentar disease forms. The results unveiled the presence of MMP-2 and MMP-9 in both species, albeit with distinct localization patterns. Specifically, MMP-9 exhibited significantly higher gelatinolytic activity in La when compared to Lb. Moreover, our data cleverly illustrated the presence and release of MMP-2 and MMP-9 by La and Lb promastigotes, exposing their ability to invade and migrate within a collagen matrix. This pioneering study establishes a compelling correlation between MMP-2 and MMP-9 and their potential role in the dynamics of La and Lb infection. Suggesting their potential as prognostic markers for severe leishmaniasis and promising target molecules for therapeutic interventions, this research opens new avenues for combatting this debilitating parasitic disease.

摘要

金属蛋白酶(MMPs)是一类显著的锌依赖性内肽酶,对于降解细胞外基质的成分至关重要,从而积极影响细胞迁移。它们对细胞内寄生虫的影响,如神秘的原生动物利什曼原虫,引发了有趣的疑问。本研究探索了 MMP-2 和 MMP-9 在利什曼原虫属(spp.)前鞭毛体中的未开发领域。值得注意的是,我们成功地检测和定量了这些 MMPs,同时还评估了它们在两种不同的利什曼原虫物种(L. amazonensis [La] 和 L. braziliensis [Lb])在不同生长阶段和从不同临床皮肤疾病形式中分离出来的活性。结果揭示了 MMP-2 和 MMP-9 在这两个物种中的存在,尽管存在明显的定位模式。具体而言,MMP-9 在 La 中的明胶酶活性明显高于 Lb。此外,我们的数据巧妙地说明了 La 和 Lb 前鞭毛体的 MMP-2 和 MMP-9 的存在和释放,暴露了它们在胶原基质中入侵和迁移的能力。这项开创性的研究在 La 和 Lb 感染的动态中建立了 MMP-2 和 MMP-9 之间的有力相关性及其潜在作用。提示它们作为严重利什曼病的预后标志物和治疗干预的有前途的靶标分子的潜力,该研究为对抗这种使人衰弱的寄生虫病开辟了新的途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df2c/10428646/d814f0782ae4/12866_2023_2973_Fig1_HTML.jpg

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