Mast cell degranulation-triggered by SARS-CoV-2 induces tracheal-bronchial epithelial in fl ammation and injury

	Mast cell degranulation-triggered by SARS-CoV-2 induces tracheal-bronchial epithelial in fl ammation and injury
	Cao, JB; Zhu, ST; Huang, XS; Wang, XY; Wu, ML; Li, X; Liu, FL; Chen, L; Zheng, YT; Wang, JH
	2024
发表期刊	VIROLOGICA SINICA
ISSN	1674-0769
卷号	39 期号:2 页码:309-318
摘要	SARS-CoV-2 infection-induced hyper-inflammation is a key pathogenic factor of COVID-19. Our research, along with others', has demonstrated that mast cells (MCs) play a vital role in the initiation of hyper-inflammation caused by SARS-CoV-2. In previous study, we observed that SARS-CoV-2 infection induced the accumulation of MCs in the peri-bronchus and bronchioalveolar-duct junction in humanized mice. Additionally, we found that MC degranulation triggered by the spike protein resulted in inflammation in alveolar epithelial cells and capillary endothelial cells, leading to subsequent lung injury. The trachea and bronchus are the routes for SARS-CoV-2 transmission after virus inhalation, and inflammation in these regions could promote viral spread. MCs are widely distributed throughout the respiratory tract. Thus, in this study, we investigated the role of MCs and their degranulation in the development of inflammation in tracheal-bronchial epithelium. Histological analyses showed the accumulation and degranulation of MCs in the peri-trachea of humanized mice infected with SARS-CoV-2. MC degranulation caused lesions in trachea, and the formation of papillary hyperplasia was observed. Through transcriptome analysis in bronchial epithelial cells, we found that MC degranulation significantly altered multiple cellular signaling, particularly, leading to upregulated immune responses and inflammation. The administration of ebastine or loratadine effectively suppressed the induction of inflammatory factors in bronchial epithelial cells and alleviated tracheal injury in mice. Taken together, our findings confirm the essential role of MC degranulation in SARS-CoV-2-induced hyper-inflammation and the subsequent tissue lesions. Furthermore, our results support the use of ebastine or loratadine to inhibit SARS-CoV-2-triggered degranulation, thereby preventing tissue damage caused by hyper-inflammation.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14206
专题	科研部门_分子免疫药理学（郑永唐）
推荐引用方式 GB/T 7714	Cao, JB,Zhu, ST,Huang, XS,et al. Mast cell degranulation-triggered by SARS-CoV-2 induces tracheal-bronchial epithelial in fl ammation and injury[J]. VIROLOGICA SINICA,2024,39(2):309-318.
APA	Cao, JB.,Zhu, ST.,Huang, XS.,Wang, XY.,Wu, ML.,...&Wang, JH.(2024).Mast cell degranulation-triggered by SARS-CoV-2 induces tracheal-bronchial epithelial in fl ammation and injury.VIROLOGICA SINICA,39(2),309-318.
MLA	Cao, JB,et al."Mast cell degranulation-triggered by SARS-CoV-2 induces tracheal-bronchial epithelial in fl ammation and injury".VIROLOGICA SINICA 39.2(2024):309-318.

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