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首页> 外文期刊>Infection and immunity >High Matrix Metalloproteinase Production Correlates with Immune Activation and Leukocyte Migration in Leprosy Reactional Lesions
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High Matrix Metalloproteinase Production Correlates with Immune Activation and Leukocyte Migration in Leprosy Reactional Lesions

机译：基质金属蛋白酶的高产量与麻风反应性病变中的免疫激活和白细胞迁移有关。

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Gelatinases A and B (matrix metalloproteinase 2 [MMP-2] and MMP-9, respectively) can induce basal membrane breakdown and leukocyte migration, but their role in leprosy skin inflammation remains unclear. In this study, we analyzed clinical specimens from leprosy patients taken from stable, untreated skin lesions and during reactional episodes (reversal reaction [RR] and erythema nodosum leprosum [ENL]). The participation of MMPs in disease was suggested by (i) increased MMP mRNA expression levels in skin biopsy specimens correlating with the expression of gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α), (ii) the detection of the MMP protein and enzymatic activity within the inflammatory infiltrate, (iii) increased MMP levels in patient sera, and (iv) the in vitro induction of MMP-9 by Mycobacterium leprae and/or TNF-α. It was observed that IFN-γ, TNF-α, MMP-2, and MMP-9 mRNA levels were higher in tuberculoid than lepromatous lesions. In contrast, interleukin-10 and tissue inhibitor of MMP (TIMP-1) message were not differentially modulated. These data correlated with the detection of the MMP protein evidenced by immunohistochemistry and confocal microscopy. When RR and ENL lesions were analyzed, an increase in TNF-α, MMP-2, and MMP-9, but not TIMP-1, mRNA levels was observed together with stronger MMP activity (zymography/in situ zymography). Moreover, following in vitro stimulation of peripheral blood cells, M. leprae induced the expression of MMP-9 (mRNA and protein) in cultured cells. Overall, the present data demonstrate an enhanced MMP/TIMP-1 ratio in the inflammatory states of leprosy and point to potential mechanisms for tissue damage. These results pave the way toward the application of new therapeutic interventions for leprosy reactions.
机译：明胶酶A和B（分别为基质金属蛋白酶2 [MMP-2]和MMP-9）可以诱导基底膜分解和白细胞迁移，但是它们在麻风性皮肤炎症中的作用仍不清楚。在这项研究中，我们分析了来自麻风病患者的临床标本，这些标本取自未经治疗的稳定皮肤病变以及在反应发作期间（逆反应[RR]和结节性红斑麻风病[ENL]）。 MMPs参与疾病的提示是：（i）皮肤活检标本中MMP mRNA表达水平的升高与γ-干扰素（IFN-γ）和肿瘤坏死因子α（TNF-α）的表达相关;（ii）检测炎症浸润液中的MMP蛋白和酶活性，（iii）患者血清中MMP水平升高，以及（iv）麻风分枝杆菌和/或TNF-α体外诱导MMP-9。观察到结核病中的IFN-γ，TNF-α，MMP-2和MMP-9 mRNA水平高于麻风病灶。相比之下，白介素10和MMP的组织抑制剂（TIMP-1）信息未得到差异调节。这些数据与免疫组织化学和共聚焦显微镜证实的MMP蛋白的检测有关。分析RR和ENL病变时，观察到TNF-α，MMP-2和MMP-9的增加，但未观察到TIMP-1，mRNA的水平以及更强的MMP活性（酶谱/原位酶谱）。此外，在体外刺激外周血细胞后，麻风分枝杆菌诱导了培养细胞中MMP-9（mRNA和蛋白质）的表达。总的来说，目前的数据表明麻风炎状态的MMP / TIMP-1比值增加，并指出了组织损伤的潜在机制。这些结果为麻风反应的新治疗手段的应用铺平了道路。

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