ArticleInternational journal of molecular sciences2020
Blocking ADAM17 Function with a Monoclonal Antibody Improves Sepsis Survival in a Murine Model of Polymicrobial Sepsis.
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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The trial behind it
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Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- Prognostic value of miR-26b-5p in prostate cancer and its regulatory effect on tumor progression.World journal of surgical oncology · 2026Article
- Targeting IL-6 trans-signalling: past, present and future prospects.Nature reviews. Immunology · 2023Review
- Recent Advances in Monoclonal Antibody-Based Approaches in the Management of Bacterial Sepsis.Biomedicines · 2023Review
- Immune Responses to IAV Infection and the Roles of L-Selectin and ADAM17 in Lymphocyte Homing.Pathogens (Basel, Switzerland) · 2022Review
- Examination of IgG Fc Receptor CD16A and CD64 Expression by Canine Leukocytes and Their ADCC Activity in Engineered NK Cells.Frontiers in immunology · 2022Article
- An ADAM17-Neutralizing Antibody Reduces Inflammation and Mortality While Increasing Viral Burden in a COVID-19 Mouse Model.Frontiers in immunology · 2022Article
- The ADAM17-directed Inhibitory Antibody MEDI3622 Antagonizes Radiotherapy-induced VEGF Release and Sensitizes Non-Small Cell Lung Cancer for Radiotherapy.Cancer research communications · 2021Article
- A Disintegrin and Metalloproteases (ADAMs): Activation, Regulation and Mechanisms of Catalysis.International journal of molecular sciences · 2021Article
- Activation of ADAM17 by IL-15 Limits Human NK Cell Proliferation.Frontiers in immunology · 2021Article
- Ectodomain shedding by ADAM17 (a disintegrin and metalloproteinase 17) in canine neutrophils.Veterinary immunology and immunopathology · 2021Article
- A Disintegrin and Metalloproteinase-Control Elements in Infectious Diseases.Frontiers in cardiovascular medicine · 2020Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Sepsis is the culmination of hyperinflammation and immune suppression in response to severe infection. Neutrophils are critical early responders to bacterial infection but can become highly dysfunctional during sepsis and other inflammatory disorders. The transmembrane protease ADAM17 (a disintegrin and metalloproteinase 17) is expressed by leukocytes and most other cells and has many substrates that regulate inflammation. We have reported that conditional knockout mice lacking ADAM17 in all leukocytes had a survival advantage during sepsis, which was associated with improved neutrophil effector functions. These and other findings indicate aberrant ADAM17 activity during sepsis. For this study, we evaluated for the first time the effects of an ADAM17 function blocking monoclonal antibody (mAb) on the pathogenesis of polymicrobial sepsis. Mice treated with the ADAM17 mAb MEDI3622 prior to sepsis induction exhibited significantly decreased mortality. When the ADAM17 mAb was combined with antibiotic administration, sepsis survival was markedly enhanced compared to either intervention alone, which was associated with a significant reduction in plasma levels of various inflammation-related factors. MEDI3622 and antibiotic administration after sepsis induction also significantly improved survival. Our results indicate that the combination of blocking ADAM17 as an immune modulator and appropriate antibiotics may provide a new therapeutic avenue for sepsis treatment.
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Registered trials
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