ArticleAmerican journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons2021
Alpha-1 antitrypsin suppresses macrophage activation and promotes islet graft survival after intrahepatic islet transplantation.
Article in American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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The trial behind it
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Who cites it
22 citing papers in PubMed, 27 citations in OpenAlex.
- Alpha-1 Antitrypsin Augmentation Therapy in Chronic Pancreatitis Patients Undergoing Total Pancreatectomy and Islet Autotransplantation: A Randomized, Controlled Study.Cell transplantationTrial
- Human α1-Antitrypsin Inhibits Nociceptor Excitability and Relieves Inflammatory and Neuropathic Pain.Biomolecules · 2026Article
- The Serpin Superfamily in Adipose Tissue Remodeling: Molecular Drivers of Immune-Metabolic Crosstalk and Insulin Sensitivity.Biology · 2026Review
- Enhancing islet transplantation outcomes in T1DM: The promise of mesenchymal stem cells and exosomes.International journal of pharmaceutics: X · 2026Review
- Glycated and Non-Glycated Human Alpha-1 Antitrypsin in Hyperglycemic Wound Healing: In Vivo and In Vitro Models.Biology · 2026Article
- Alpha-1 antitrypsin as a new biomarker of inflammation, infection and disease severity in community-acquired pneumonia: a prospective cohort study.Scientific reports · 2026Article
- Alpha-1 Antitrypsin Mediates Spontaneous Resolution of Acute Gouty Inflammation Via Inhibiting Caspase 3/GSDME-dependent Macrophage Pyroptosis.Inflammation · 2025Article
- Role of Transcription Factor, LIM Homeobox 9 (LHX9) in Inflammatory Response by PGE2 and Thrombin in SERPINA1-Silencing Endometrial Stromal Cells.Molecular reproduction and development · 2025Article
- Review
- Macrophage polarization: molecular mechanisms, disease implications, and targeted therapeutic strategies.Frontiers in immunology · 2025Review
- Exploring the molecular mechanisms of macrophages in islet transplantation using single-cell analysis.Frontiers in immunology · 2024Article
- Interaction of Iron Oxide Nanoparticles with Macrophages Is Influenced Distinctly by "Self" and "Non-Self" Biological Identities.ACS applied materials & interfaces · 2023Article
- Advancements in innate immune regulation strategies in islet transplantation.Frontiers in immunology · 2023Review
- Stem Cell Therapy Improves Human Islet Graft Survival in Mice via Regulation of Macrophages.Diabetes · 2022Article
- Alpha 1 Antitrypsin Regulates Trophoblast Syncytialization and Inflammatory Factor Expression.International journal of molecular sciences · 2022Article
- Single-Cell Landscape of Mouse Islet Allograft and Syngeneic Graft.Frontiers in immunology · 2022Article
- The Influence of Microenvironment on Survival of Intraportal Transplanted Islets.Frontiers in immunology · 2022Review
- Immune-Protective Formulations and Process Strategies for Improved Survival and Function of Transplanted Islets.Frontiers in immunology · 2022Review
- Toll-like receptor signaling pathway triggered by inhibition of serpin A1 stimulates production of inflammatory cytokines by endometrial stromal cells.Frontiers in endocrinology · 2022Article
- What Is New with Total Pancreatectomy and Autologous Islet Cell Transplantation? Review of Current Progress in the Field.Journal of clinical medicine · 2021Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Alpha-1 antitrypsin (AAT) has protective functions in animal islet transplantation models. While the therapeutic effect of AAT therapy is currently being tested in clinical trials, we investigated the mechanism of AAT protection in a clinically relevant marginal intrahepatic human islet transplantation model. In recipients receiving islets and AAT, 68.9% (20/29) reached normoglycemia, compared to 35.7% (10/28) in those receiving islets only, at 60 days posttransplant (PT). AAT-treated mice had lower serum levels of inflammatory cytokines immediately PT. Reduced M1 macrophages were observed in livers of AAT-treated recipients compared to controls as evidenced by flow cytometry and RNA-seq transcriptional profiling analysis. In vitro AAT suppressed IFN-γ-induced M1 macrophage activation/polarization via suppression of STAT1 phosphorylation and iNOS production. AAT inhibits macrophage activation induced by cytokines or dying islets, and consequently leads to islet cell survival. In a macrophage depletion mouse model, the presence of M1 macrophages in the liver contributed to graft death. AAT, through suppressing macrophage activation, protected transplanted islets from death and dysfunction in the human islet and NOD-SCID mouse model. The protective effect of AAT was confirmed in a major mismatch allogeneic islet transplantation model. Taken together, AAT suppresses liver macrophage activation that contributes to graft survival after transplantation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.