Mast cell activation in lungs during SARS-CoV-2 infection associated with lung pathology and severe COVID-19.
Mast cell activation in lungs during SARS-CoV-2 infection associated with lung pathology and severe COVID-19.
复制标题
SARS-COV-2感染期间肺部的肥大细胞激活与肺病理学和严重的Covid-19。
DOI：
10.1172/jci149834
复制
发表时间：
2023-10-02
影响因子：
15.9
通讯作者：
St John, Ashley L.
中科院分区：
文献类型：
--
作者：
Tan, Janessa Y. J.;Anderson, Danielle E.;Rathore, Abhay P. S.;O'Neill, Aled;Mantri, Chinmay Kumar;Saron, Wilfried A. A.;Lee, Cheryl Q. E.;Cui, Chu Wern;Kang, Adrian E. Z.;Foo, Randy;Kalimuddin, Shirin;Low, Jenny G.;Ho, Lena;Tambyah, Paul;Burke, Thomas W.;Woods, Christopher W.;Chan, Kuan Rong;Karhausen, Jorn;St John, Ashley L.
肺部炎症是重症患者2019冠状病毒病（COVID-19）的一个标志，疾病的病理生理被认为是免疫介导的。肥大细胞（MCs）是存在于气道中的多功能免疫细胞，它们对某些病毒和过敏原作出反应，并经常促进炎症。我们在sars - cov -2感染的小鼠和非人灵长类动物中观察到急性和未解决的气道炎症期间MCs广泛脱颗粒。利用小鼠MC缺乏症模型，在SARS-CoV-2感染期间观察到MC依赖性间质性肺炎、肺出血和水肿。在人类中，需要补充氧气的患者的转录变化也涉及严重疾病中具有MC表型的细胞。通过检测MC特异性蛋白酶（包括乳糜酶），证实了MC在人体内的激活，其水平与疾病严重程度和血管失调的生物标志物显著相关。这些结果支持动物模型中MCs参与SARS-CoV-2感染期间的肺组织损伤，以及MCs激活与人类严重COVID-19之间的关联，提出了潜在的干预策略。
Lung inflammation is a hallmark of Coronavirus disease 2019 (COVID-19) in patients who are severely ill, and the pathophysiology of disease is thought to be immune mediated. Mast cells (MCs) are polyfunctional immune cells present in the airways, where they respond to certain viruses and allergens and often promote inflammation. We observed widespread degranulation of MCs during acute and unresolved airway inflammation in SARS-CoV-2-infected mice and nonhuman primates. Using a mouse model of MC deficiency, MC-dependent interstitial pneumonitis, hemorrhaging, and edema in the lung were observed during SARS-CoV-2 infection. In humans, transcriptional changes in patients requiring oxygen supplementation also implicated cells with a MC phenotype in severe disease. MC activation in humans was confirmed through detection of MC-specific proteases, including chymase, the levels of which were significantly correlated with disease severity and with biomarkers of vascular dysregulation. These results support the involvement of MCs in lung tissue damage during SARS-CoV-2 infection in animal models and the association of MC activation with severe COVID-19 in humans, suggesting potential strategies for intervention.