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人类严重登革热肾组织中细胞间黏附分子-1 和血管细胞黏附分子-1 的上调:对内皮细胞激活/功能障碍的影响。

Upregulation of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in renal tissue in severe dengue in humans: Effects on endothelial activation/dysfunction.

机构信息

Universidade de São Paulo, Faculdade de Medicina, Laboratório da Disciplina de Patologia de Moléstias Transmissíveis, São Paulo, SP, Brasil.

Instituto de Assistência Médica ao Servidor Público Estadual, Programa de Pós-Graduação em Ciências da Saúde, São Paulo, SP, Brasil.

出版信息

Rev Soc Bras Med Trop. 2019 Nov 14;52:e20180353. doi: 10.1590/0037-8682-0353-2018. eCollection 2019.

DOI:10.1590/0037-8682-0353-2018
PMID:31778418
Abstract

INTRODUCTION

Dengue is an important mosquito-borne disease in tropical and subtropical regions. Adhesion molecules have not been systematically characterized in the renal tissue of patients with severe dengue (SD). The objective of this study was to detect viral antigens in samples from patients that evolved with SD, correlating with the expression of ICAM-1, VCAM-1, VE-cadherin, and E-selectin to contribute to a better understanding of the pathophysiology of SD.

METHODS

Kidney specimens from patients with SD were selected according to clinical and laboratorial data and submitted to histological and immunohistochemistry analysis. A semiquantitative evaluation was performed considering positive immunostaining in 20 glomeruli.

RESULTS

Viral antigens were mainly detected in distal tubules. The intense immunostaining of VCAM-1 and ICAM-1 was observed. The expression of E-selectin was discrete, and VE-cadherin expression varied from mild to moderate. VCAM-1 was slightly intense in the glomerular capsule; the expression of ICAM-1 was diffuse. E-selectin was diffuse, and VE-cadherin varied from mild to moderate. The most frequent histological findings were glomerular congestion, mild glomerulitis, acute renal injury, and glomerular atrophy.

CONCLUSIONS

The results appear to demonstrate an imbalance between vascular endothelial permeability regulating events in renal lesions in SD. The increase in the expression of ICAM-1 and VCAM-1 is an in-situ indicator of higher permeability with a consequent influx of cells favoring the inflammation of the endothelium. These molecules are important in the pathophysiology of the disease and provide the possibility of developing new markers for the evaluation, clinical follow-up, and therapeutic response of patients with SD.

摘要

简介

登革热是热带和亚热带地区重要的蚊媒疾病。粘附分子在重症登革热(SD)患者的肾组织中尚未得到系统表征。本研究的目的是检测在进展为 SD 的患者样本中的病毒抗原,并与 ICAM-1、VCAM-1、VE-钙粘蛋白和 E-选择素的表达相关联,以帮助更好地理解 SD 的病理生理学。

方法

根据临床和实验室数据选择 SD 患者的肾组织标本,并进行组织学和免疫组织化学分析。通过对 20 个肾小球的阳性免疫染色进行半定量评估。

结果

病毒抗原主要在远曲小管中检测到。观察到 VCAM-1 和 ICAM-1 的强烈免疫染色。E-选择素的表达不明显,VE-钙粘蛋白的表达从轻度到中度不等。肾小球囊的 VCAM-1 表达略强;ICAM-1 的表达弥漫性。E-选择素弥漫性,VE-钙粘蛋白从轻度到中度不等。最常见的组织学发现是肾小球淤血、轻度肾小球肾炎、急性肾损伤和肾小球萎缩。

结论

结果似乎表明在 SD 肾病变中血管内皮通透性调节事件之间存在不平衡。ICAM-1 和 VCAM-1 的表达增加是通透性增加的原位指标,导致细胞流入,有利于内皮炎症。这些分子在疾病的病理生理学中很重要,并为评估、临床随访和 SD 患者的治疗反应提供了开发新标志物的可能性。

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