ArticleProceedings of the National Academy of Sciences of the United States of America2005
Alpha1-antitrypsin monotherapy prolongs islet allograft survival in mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
102 citing papers in PubMed, 176 citations in OpenAlex.
- A randomized controlled pilot trial of etanercept and alpha-1 antitrypsin to improve autologous islet engraftment.Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] · 2023Trial
- Human plasma-derived alphaPediatric diabetes · 2021Trial
- A Phase II, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study Evaluating the Efficacy and Safety of Alpha-1 Antitrypsin (AAT) (GlassiaInternational journal of molecular sciences · 2019Trial
- αBlood · 2018Trial
- Alpha-1 Antitrypsin Augmentation Therapy in Chronic Pancreatitis Patients Undergoing Total Pancreatectomy and Islet Autotransplantation: A Randomized, Controlled Study.Cell transplantationTrial
- Polymeric alpha-1 antitrypsin perturbs Paneth cell proteostasis and exacerbates intestinal inflammation.Signal transduction and targeted therapy · 2026Article
- Taming autoimmunity: Alpha-1 antitrypsin overexpressing mesenchymal stromal cells promote regulatory T cell crosstalk to reverse diabetes.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Glycated and Non-Glycated Human Alpha-1 Antitrypsin in Hyperglycemic Wound Healing: In Vivo and In Vitro Models.Biology · 2026Article
- Alpha-1 Antitrypsin Protects Against Cisplatin-Induced Acute Kidney Injury by Restoring Redox and Mitochondrial Homeostasis.Biomolecules · 2026Article
- Review
- Analysis of alpha-1-antitrypsin (AAT)-regulated, glucocorticoid receptor-dependent genes in macrophages reveals a novel host defense function of AAT.Physiological reports · 2024Article
- Immunological and homeostatic pathways of alpha -1 antitrypsin: a new therapeutic potential.Frontiers in immunology · 2024Review
- Type 1 diabetes contributes to combined pulmonary fibrosis and emphysema in male alpha 1 antitrypsin deficient mice.PloS one · 2023Article
- Role and mechanism of alpa1-antitrypsin in polycystic ovary syndrome.Saudi medical journal · 2022Article
- Mechanisms Linking COPD to Type 1 and 2 Diabetes Mellitus: Is There a Relationship between Diabetes and COPD?Medicina (Kaunas, Lithuania) · 2022Review
- Pancreas Preservation with a Neutrophil Elastase Inhibitor, Alvelestat, Contributes to Improvement of Porcine Islet Isolation and Transplantation.Journal of clinical medicine · 2022Article
- Comparison of alpha 1- antitrypsin activity and phenotype in type 1 diabetic patients to healthy individuals.Journal of family medicine and primary care · 2022Article
- Ceruletide and Alpha-1 Antitrypsin as a Novel Combination Therapy for Ischemic Stroke.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Article
- A Review of Alpha-1 Antitrypsin Binding Partners for Immune Regulation and Potential Therapeutic Application.International journal of molecular sciences · 2022Review
- The Role of Proteases and Serpin Protease Inhibitors in β-Cell Biology and Diabetes.Biomolecules · 2022Review
42 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Islet transplantation for type 1 diabetic patients shows promising results with the use of nondiabetogenic immunosuppressive therapy. However, in addition to compromising the immune system of transplant recipients, long-term studies demonstrate that islet viability is impaired. Here, we demonstrate that, in the absence of immunosuppressive agents, monotherapy with clinical-grade human alpha1-antitrypsin (hAAT), the major serum serine-protease inhibitor, prolongs islet graft survival and normoglycemia in transplanted allogeneic diabetic mice, lasting until the development of anti-hAAT antibodies. Compared to untreated or albumin-control-treated graft recipients, which rejected islets at day 10, AAT-treated mice displayed diminished cellular infiltrates and intact intragraft insulin production throughout treatment. Using peritoneal infiltration models, we demonstrate that AAT decreases allogeneic fibroblast-elicited natural-killer-cell influx by 89%, CD3-positive cell influx by 44%, and thioglycolate-elicited neutrophil emigration by 66%. ATT also extended islet viability in mice after streptozotocin-induced beta cell toxicity. In vitro, several islet responses to IL-1beta/IFNgamma stimulation were examined. In the presence of AAT, islets displayed enhanced viability and inducible insulin secretion. Islets also released 36% less nitric oxide and 82% less macrophage inflammatory protein 1 alpha and expressed 63% fewer surface MHC class II molecules. TNFalpha release from IL-1beta/IFNgamma-stimulated islet cells was reduced by 99%, accompanied by an 8-fold increase in the accumulation of membrane TNFalpha on CD45-positive islet cells. In light of the established safety record and the nondiabetogenic potential of AAT, these data suggest that AAT may be beneficial as adjunctive therapy in patients undergoing islet 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.