Mast cells promote viral entry of SARS-CoV-2 via formation of chymase/spike protein complex.
Mast cells promote viral entry of SARS-CoV-2 via formation of chymase/spike protein complex.
复制标题
DOI：
10.1016/j.ejphar.2022.175169
复制
发表时间：
2022-09-05
影响因子：
5
通讯作者：
Mogi, Masaki
中科院分区：
文献类型：
--
作者：
Liu, Shuang;Suzuki, Yasuyuki;Takemasa, Erika;Watanabe, Ryusuke;Mogi, Masaki
与严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 相关的肺部病理结果是由于多种促炎细胞因子的释放造成的，从而导致肺部的后续损伤。目前的研究旨在从病毒进入的角度研究肥大细胞对病毒接种的反应及其对宿主防御的贡献。掺入了 SARS-CoV-2 刺突糖蛋白的假病毒粒子触发了肥大细胞的激活，而肥大细胞来源的食糜酶 MCP2 与刺突蛋白形成了复合物，促进了蛋白酶依赖性病毒进入。根据病毒进入的定量结果，与未处理的细胞相比，10 μM 槲皮素（一种肥大细胞稳定剂）可有效抑制 41.3% 的病毒进入，而 100 μM 糜抑素（作为食糜酶抑制剂）可抑制 52.1% 的病毒进入。使用肥大细胞缺陷小鼠的研究表明，肥大细胞的缺失可能会影响上呼吸道的早期病毒载量，从而增加病毒侵入下呼吸道系统的风险。此外，肥大细胞缺陷小鼠在病毒接种后的后期表现出持续感染，而在野生型小鼠中观察到病毒阳性细胞的清除。总之，肥大细胞作为一种多方面的免疫调节剂，对 SARS-CoV-2 的病毒进入具有保护作用和致病性影响。应根据感染阶段和细胞因子风暴的风险优化肥大细胞稳定剂和食糜酶抑制剂在治疗 SARS-CoV-2 诱导的急性呼吸综合征中的效用。
The pulmonary pathological findings associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) result from the release of multiple proinflammatory cytokines, which causes the subsequential damage of the lungs. The current study was undertaken to investigate the responses of mast cells to viral inoculation and their contribution to host defenses from the point of view of viral entry. Pseudovirions, in which the spike glycoprotein of SARS-CoV-2 was incorporated, triggered activation of mast cells, and a mast cell-derived chymase, MCP2, formed a complex with spike protein, which promoted protease-dependent viral entry. According to the quantification results of viral entry, 10 μM quercetin, a mast cell stabilizer, potentially potently inhibited 41.3% of viral entry, while 100 μM chymostatin, which served as a chymase inhibitor, suppressed 52.1% of viral entry, compared to non-treated cells. Study using mast cell-deficient mice showed that the absence of mast cells may influence early viral loading in the upper respiratory tract, which consequently increases the risk of viral invasion into the lower respiratory system. Furthermore, mast cell-deficient mice exhibited ongoing infection in the late phase post-viral inoculation, while clearance of virus-positive cells was observed in wild-type mice. In conclusion, mast cells act as a multifaceted immune modulator that is equipped with both protective effects and pathogenic influences on viral entry of SARS-CoV-2. The utility of mast cell stabilizers and chymase inhibitors in the treatment of SARS-CoV-2-induced acute respiratory syndrome should be optimized regarding the infection stage and the risk of cytokine storm.
登录
查看更多内容
DOI：
10.1016/j.bbadis.2010.12.014
发表时间：
2012-01
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Theoharides TC;Alysandratos KD;Angelidou A;Delivanis DA;Sismanopoulos N;Zhang B;Asadi S;Vasiadi M;Weng Z;Miniati A;Kalogeromitros D
通讯作者：
Kalogeromitros D
CRACM3通过与语法的分子相互作用来调节Ca（2+）独立方式中不可驱动的胞囊囊泡融合孔的稳定性。
影响因子：
4.6
作者：
Liu S;Sahid MN;Takemasa E;Kiyoi T;Kuno M;Oshima Y;Maeyama K
通讯作者：
Maeyama K
转录分析证实了登革热疾病模型中肥大细胞稳定的治疗作用。
影响因子：
5.4
作者：
Morrison J;Rathore APS;Mantri CK;Aman SAB;Nishida A;St John AL
通讯作者：
St John AL
影响因子：
13.2
作者：
Chan, Jasper Fuk-Woo;Kok, Kin-Hang;Yuen, Kwok-Yung
通讯作者：
Yuen, Kwok-Yung
影响因子：
5.4
作者：
Glowacka, Ilona;Bertram, Stephanie;Poehlmann, Stefan
通讯作者：
Poehlmann, Stefan