An ADAM17-Neutralizing Antibody Reduces Inflammation and Mortality While Increasing Viral Burden in a COVID-19 Mouse Model.

Autor:	Hedges JF; Department of Microbiology and Cell Biology, Montana State University, Bozeman, MT, United States., Snyder DT; Department of Microbiology and Cell Biology, Montana State University, Bozeman, MT, United States., Robison A; Department of Microbiology and Cell Biology, Montana State University, Bozeman, MT, United States., Grifka-Walk HM; Department of Microbiology and Cell Biology, Montana State University, Bozeman, MT, United States., Blackwell K; Department of Microbiology and Cell Biology, Montana State University, Bozeman, MT, United States., Shepardson K; Department of Microbiology and Cell Biology, Montana State University, Bozeman, MT, United States., Kominsky D; Department of Microbiology and Cell Biology, Montana State University, Bozeman, MT, United States., Rynda-Apple A; Department of Microbiology and Cell Biology, Montana State University, Bozeman, MT, United States., Walcheck B; Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN, United States., Jutila MA; Department of Microbiology and Cell Biology, Montana State University, Bozeman, MT, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Jun 10; Vol. 13, pp. 918881. Date of Electronic Publication: 2022 Jun 10 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.918881
Abstrakt:	Angiotensin Converting Enzyme 2 (ACE2) is the primary cell entry receptor for SARS-CoV and SARS-CoV-2 viruses. A disintegrin and metalloproteinase 17 (ADAM17) is a protease that cleaves ectodomains of transmembrane proteins, including that of ACE2 and the proinflammatory cytokine TNF-α, from cell surfaces upon cellular activation. We hypothesized that blockade of ADAM17 activity would alter COVID-19 pathogenesis. To assess this pathway, we blocked the function of ADAM17 using the monoclonal antibody MEDI3622 in the K18-hACE2 transgenic mouse model of COVID-19. Antibody-treated mice were healthier, less moribund, and had significantly lower lung pathology than saline-treated mice. However, the viral burden in the lungs of MEDI3622-treated mice was significantly increased. Thus, ADAM17 appears to have a critical anti-viral role, but also may promote inflammatory damage. Since the inflammatory cascade is ultimately the reason for adverse outcomes in COVID-19 patients, there may be a therapeutic application for the MEDI3622 antibody. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Hedges, Snyder, Robison, Grifka-Walk, Blackwell, Shepardson, Kominsky, Rynda-Apple, Walcheck and Jutila.)
Databáze:	MEDLINE
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