ArticlePloS one2017
Serum α-1 Antitrypsin (AAT) antagonizes intrinsic apoptosis induction in neutrophils from patients with systemic inflammatory response syndrome.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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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
14 citing papers in PubMed, 13 citations in OpenAlex.
- The "Double-Edged Sword" of Neutrophils in Trauma: From Pathophysiological Mechanisms to Precision Immunomodulation Strategies.International journal of molecular sciences · 2026Review
- The Role of Alpha-1 Antitrypsin in the Pathophysiology and Treatment of Inflammatory Lung Diseases.Journal of inflammation research · 2026Review
- Article
- Immunological and homeostatic pathways of alpha -1 antitrypsin: a new therapeutic potential.Frontiers in immunology · 2024Review
- Accelerated Wound Border Closure Using a Microemulsion Containing Non-Inhibitory Recombinant α1-Antitrypsin.International journal of molecular sciences · 2022Article
- Complement Factor C5a Inhibits Apoptosis of Neutrophils-A Mechanism in Polytrauma?Journal of clinical medicine · 2021Article
- The Serpin Superfamily and Their Role in the Regulation and Dysfunction of Serine Protease Activity in COPD and Other Chronic Lung Diseases.International journal of molecular sciences · 2021Review
- Damage-associated molecular patterns in trauma.European journal of trauma and emergency surgery : official publication of the European Trauma Society · 2020Review
- Alpha1-antitrypsin protects lung cancer cells from staurosporine-induced apoptosis: the role of bacterial lipopolysaccharide.Scientific reports · 2020Article
- Mechanisms behind Retinal Ganglion Cell Loss in Diabetes and Therapeutic Approach.International journal of molecular sciences · 2020Review
- Activation of death-associated protein kinase 1 promotes neutrophil apoptosis to accelerate inflammatory resolution in acute respiratory distress syndrome.Laboratory investigation; a journal of technical methods and pathology · 2019Article
- S-Nitrosylation of α1-Antitrypsin Triggers Macrophages Toward Inflammatory Phenotype and Enhances Intra-Cellular Bacteria Elimination.Frontiers in immunology · 2019Article
- The Multifaceted Effects of Alpha1-Antitrypsin on Neutrophil Functions.Frontiers in pharmacology · 2018Review
- cfDNA correlates with endothelial damage after cardiac surgery with prolonged cardiopulmonary bypass and amplifies NETosis in an intracellular TLR9-independent manner.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Excessive neutrophil activation accompanied by delayed apoptotic cell death in inflammatory conditions causes progressive damage of cells and tissues, leading to life-threatening multiple organ dysfunction syndrome. Previous work suggested that circulating serum factors during inflammation are critically involved in the suppression of neutrophil cell death although the identity of these antiapoptotic mediators remained elusive. In this study, we identified the acute phase protein α-1 Antitrypsin (AAT) as a potent suppressor of staurosporine (STS)-induced apoptosis in human neutrophils through a mechanism implicating caspases-independent pathways. We show here that serum levels of AAT, potentially in part released by stimulated neutrophils, are markedly elevated in major trauma patients suffering from systemic inflammatory response syndrome (SIRS). Notably, AAT depletion from serum increased sensitivity of human neutrophils for STS-induced cell death. In fact, AAT was demonstrated to confer intrinsic apoptosis resistance by preventing PKC/Akt inactivation and subsequent proteasomal degradation of antiapoptotic Mcl-1 protein in response to STS treatment. Neither MAP kinase ERK1/2 nor caspases were found to be involved in AAT-triggered antiapoptotic pathways in neutrophils. In summary, these results establish a novel pivotal role of circulating AAT in mediating survival by antagonizing the proapoptotic action of the PKC inhibitor STS and should be considered for AAT augmentation therapies in future.
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