ArticleJournal of immunology (Baltimore, Md. : 1950)2015
α1-Antitrypsin Combines with Plasma Fatty Acids and Induces Angiopoietin-like Protein 4 Expression.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
27 citing papers in PubMed, 44 citations in OpenAlex.
- Free Fatty Acids Carried by Lipoproteins: Revisiting the Overlooked Cargo.Acta physiologica (Oxford, England) · 2026Review
- Article
- Identification of Plasma Free Fatty Acid Carrier Proteins in Mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Analysis of alpha-1-antitrypsin (AAT)-regulated, glucocorticoid receptor-dependent genes in macrophages reveals a novel host defense function of AAT.Physiological reports · 2024Article
- The Inhibition of Serine Proteases by Serpins Is Augmented by Negatively Charged Heparin: A Concise Review of Some Clinically Relevant Interactions.International journal of molecular sciences · 2024Review
- α1-Antitrypsin Binds to the Glucocorticoid Receptor with Anti-Inflammatory and Antimycobacterial Significance in Macrophages.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease.Genome biology · 2021Article
- Article
- Therapeutic Potential of Alpha-1 Antitrypsin in Type 1 and Type 2 Diabetes Mellitus.Medicina (Kaunas, Lithuania) · 2021Review
- A Novel Mouse Monoclonal Antibody C42 against C-Terminal Peptide of Alpha-1-Antitrypsin.International journal of molecular sciences · 2021Article
- Post-Translational Modifications of Circulating Alpha-1-Antitrypsin Protein.International journal of molecular sciences · 2020Review
- p53's Extended Reach: The Mutant p53 Secretome.Biomolecules · 2020Review
- The Delivery of α1-Antitrypsin Therapy Through Transepidermal Route: Worthwhile to Explore.Frontiers in pharmacology · 2020Article
- Clinical Significance ofCancers · 2019Article
- Vitamin D (1,25(OH)The Journal of steroid biochemistry and molecular biology · 2019Article
- A review of the multifunctionality of angiopoietin-like 4 in eye disease.Bioscience reports · 2018Review
- Alpha-1 Antitrypsin Therapy for Autoimmune Disorders.Chronic obstructive pulmonary diseases (Miami, Fla.) · 2018Article
- Alpha-1-antitrypsin in cell and organ transplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2018Review
- Point Mutation of a Non-Elastase-Binding Site in Human α1-Antitrypsin Alters Its Anti-Inflammatory Properties.Frontiers in immunology · 2018Article
- The Multifaceted Effects of Alpha1-Antitrypsin on Neutrophil Functions.Frontiers in pharmacology · 2018Review
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 5 countries.
Funding
Abstract
α1-Antitrypsin (A1AT) purified from human plasma upregulates expression and release of angiopoietin-like protein 4 (Angptl4) in adherent human blood monocytes and in human lung microvascular endothelial cells, providing a mechanism for the broad immune-regulatory properties of A1AT independent of its antiprotease activity. In this study, we demonstrate that A1AT (Prolastin), a potent inducer of Angptl4, contains significant quantities of the fatty acids (FA) linoleic acid (C18:2) and oleic acid (C18:1). However, only trace amounts of FAs were present in preparations that failed to increase Angplt4 expression, for example, A1AT (Zemaira) or M-type A1AT purified by affinity chromatography. FA pull-down assays with Western blot analysis revealed a FA-binding ability of A1AT. In human blood-adherent monocytes, A1AT-FA conjugates upregulated expression of Angptl4 (54.9-fold, p < 0.001), FA-binding protein 4 (FABP4) (11.4-fold, p < 0.001), and, to a lesser degree, FA translocase (CD36) (3.1-fold, p < 0.001) relative to A1AT devoid of FA (A1AT-0). These latter effects of A1AT-FA were blocked by inhibitors of peroxisome proliferator-activated receptor (PPAR) β/δ (ST247) and PPARγ (GW9662). When compared with controls, cell pretreatment with ST247 diminished the effect of A1AT-LA on Angptl4 mRNA (11.6- versus 4.1-fold, p < 0.001) and FABP4 mRNA (5.4- versus 2.8-fold, p < 0.001). Similarly, preincubation of cells with GW9662 inhibited inducing effect of A1AT-LA on Angptl4 mRNA (by 2-fold, p < 0.001) and FABP4 mRNA (by 3-fold, p < 0.001). Thus, A1AT binds to FA, and it is this form of A1AT that induces Angptl4 and FABP4 expression via a PPAR-dependent pathway. These findings provide a mechanism for the unexplored area of A1AT biology independent of its antiprotease properties.
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Registered trials
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