Research reveals the new mechanism of new coronavirus-induced pneumonia injury and proposes new anti-inflammatory strategies

A joint study by the Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences and other units found that mast cells are important effector cells for the new coronavirus (SARS-CoV-2) induced lung inflammation and damage
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SARS-CoV-2 Spike protein rapidly induces mast cell degranulation by binding to the ACE2 receptor of mast cells, which in turn induces inflammation of lung epithelial cells and causes lung damage; the study also found that clinical drugs for the treatment of allergic diseases can be used as mast cell stabilizers , By preventing Spike protein from inducing degranulation of mast cells, inhibiting inflammation and protecting lung injury

The "cytokine storm" caused by SARS-CoV-2 infection is an important factor for organ damage and leading to severe illness or death
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However, the cytological mechanism of the virus-induced inflammatory factor storm in the body is still unclear, and clinical treatment lacks effective immunomodulatory methods

Mast cells are widely distributed in various mucosal and organ tissues including the respiratory tract and lungs.
They can first come into contact with allergens and pathogens, secrete a variety of cells and chemical factors, and participate in immune regulation
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The most common report of mast cells is that their degranulation is involved in related diseases such as asthma and allergies

The study found that mast cells expressing ACE2 receptor can bind to SARS-CoV-2 Spike protein, and this binding can induce mast cell degranulation within 5 minutes; Spike protein-induced mast cell degranulation can further change many types of lung epithelial cells Signaling pathways, especially inducing lung epithelial cell inflammation and destroying cell adhesion junctions; the paper uses ACE2 humanized mice and rhesus monkey infection models to prove that SARS-CoV-2 induces mast cell degranulation and its relationship with pneumonia injury It is found that SARS-CoV-2 infection in elderly monkeys (17-19 years old) can induce more lung mast cell degranulation, suggesting that SARS-CoV-2 induced mast cell activation and degranulation may be susceptible to severe illness in the elderly One of the factors
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The study found that clinical drugs for the treatment of allergic diseases, such as ebastine and loratadine, can act as mast cell stabilizers by preventing Spike protein-induced degranulation of mast cells and inhibit SARS-CoV-2 induced mice Inflammation of the lungs and protects against lung injury

The corresponding authors of the paper are Wang Jianhua, Zheng Yongtang and Chen Xinwen.
The research was supported by Zhao Jincun's team at the State Key Laboratory of Respiratory Diseases
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Henan Normal University and the Guangzhou Institute of Biomedicine and Health of the Chinese Academy of Sciences jointly trained Wu Mengli, a doctoral student, as the first author

This research was funded by the National Natural Science Foundation of China, the Open Fund of the Guangzhou State Key Laboratory of Respiratory Diseases, and the National Key Research and Development Program
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Paper link

The new coronavirus induces lung epithelial cell inflammation and causes lung damage by inducing lung mast cells to degranulate
.

SARS-CoV-2 Spike protein rapidly induces mast cell degranulation by binding to the ACE2 receptor of mast cells, which in turn induces inflammation of lung epithelial cells and leads to lung injury; clinical drugs for the treatment of allergic diseases such as ebastine and loratadine It can be used as a mast cell stabilizer by preventing Spike protein-induced degranulation of mast cells, thereby inhibiting SARS-CoV-2 induced mouse lung inflammation and protecting lung injury
.