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[新型冠状病毒感染COVID-19患者纤维化中FAP阳性活化基质细胞的定位特征]

[Localization features of FAP-positive activated stromal cells in fibrosis in patients with new coronavirus infection COVID-19].

作者信息

Danilova N V, Basalova N A, Oleynikova N A, Kelly E I, Zayratiants O V, Efimenko A Yu

机构信息

Lomonosov Moscow State University, Medical Research and Educational Institute, Moscow, Russia.

Infectious Diseases Clinical Hospital No. 1, Moscow, Russia.

出版信息

Arkh Patol. 2024;86(6):5-14. doi: 10.17116/patol2024860615.

Abstract

OBJECTIVE

To evaluate the representation and localization of FAP-positive activated stromal cells depending on the severity of fibrotic changes in tissues of patients with a confirmed diagnosis of COVID-19.

MATERIAL AND METHODS

20 autopsy observations of patients who died from COVID-19 were studied. Immunohistochemical studies were performed using antibodies to CD90, FAP and aSMA and a dual imaging system. The severity of fibrosis in lung tissue was assessed according to the R.Hubner scale (2008).

RESULTS

FAP-positive cells are detected in the lungs, kidneys, liver and myocardium, while only in the lungs FAP expression is associated with fibrotic tissue areas. FAP expression of varying intensity was observed in capillaries, alveolar and bronchial epithelium, as well as in fibrotic nodules in the lungs, where it partially colocalizes with the key myofibroblast marker aSMA. CD90-positive stromal cells were also predominantly found in fibrotic foci.

CONCLUSION

The results obtained allow us to clarify the localization of activated stromal precursors in human tissues during injury and suggest an important role of FAP in the formation of fibrotic foci and the progression of fibrotic changes in tissues, primarily the lungs, which makes it a promising pharmaceutical target for the treatment of diseases associated with the development of fibrosis.

摘要

目的

根据确诊为COVID-19患者组织纤维化改变的严重程度,评估FAP阳性活化基质细胞的表现及定位。

材料与方法

研究了20例死于COVID-19患者的尸检观察结果。使用针对CD90、FAP和α-SMA的抗体以及双成像系统进行免疫组织化学研究。根据R.Hubner量表(2008年)评估肺组织纤维化的严重程度。

结果

在肺、肾、肝和心肌中检测到FAP阳性细胞,而仅在肺中FAP表达与纤维化组织区域相关。在毛细血管、肺泡和支气管上皮以及肺中的纤维化结节中观察到不同强度的FAP表达,在这些部位它部分与关键的肌成纤维细胞标志物α-SMA共定位。CD90阳性基质细胞也主要存在于纤维化病灶中。

结论

获得的结果使我们能够阐明损伤期间人组织中活化基质前体的定位,并表明FAP在纤维化病灶形成和组织(主要是肺)纤维化改变进展中起重要作用,这使其成为治疗与纤维化发展相关疾病的有前景的药物靶点。

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