a-mouse-model-pulmonary-fibrosis-induced-nasal-bleomycin

A Mouse Model of Pulmonary Fibrosis Induced by Nasal Bleomycin Nebulization

Pulmonary fibrosis is characteristic of several human lung diseases that arise from various causes. Given that treatment options are fairly limited, mouse ...

Tianjin Chest Hospital

Acute lung injury (ALI) and resultant acute respiratory distress syndrome (ARDS) are detrimental inflammatory disease associated with high rates of morbidity and mortality due to a lack of effective treatment options. Previous study has demonstrated that an inhibition of geranylgeranyl pyrophosphate synthase large subunit 1 (GGPPS1) show a protective effect against ALI.

Catechin regulates miR-182/GGPPS1 signaling pathway and inhibits LPS-induced acute lung injury in mice.

It is unknown whether antibody-mediated enhancement (ADE) contributes to the pathogenesis of COVID-19, and the conditions for ADE needs to be elucidated. We demonstrated that without inducing an ACE2-independent ADE on Raji cells, the neutralizing antibody CB6, a mouse anti-S1 serum and convalescent plasma, induced ADE on cells expressing FcγRIIA/CD32A and low levels of endogenous ACE2. ADE occurred at sub-neutralizing antibody concentrations, indicating that unneutralized S protein was required for ADE. The enhanced infectivity of 614G variant was higher than that of 614D wildtype in the presence of antibodies, further suggesting that ADE may be influenced by virus strains with different ACE2-binding affinity. Finally, knockdown of ACE2 or treatment with a fusion-inhibition peptide EK1C4 significantly reduced ADE. In conclusion, we identified an ADE mechanism mediated by neutralizing antibodies against SARS-CoV-2. ACE2 may act as a secondary receptor required for the antibody- and FcγR-mediated enhanced entry of SARS-CoV-2.

Shengnan Yang

Tianjin Chest Hospital

A Mouse Model of Pulmonary Fibrosis Induced by Nasal Bleomycin Nebulization