Evidence map›Paper›PMID 21060150›Full record

ArticleThe Journal of clinical investigation2010

α-1 Antitrypsin regulates human neutrophil chemotaxis induced by soluble immune complexes and IL-8.

David A Bergin, Emer P Reeves, Paula Meleady, Michael Henry, Oliver J McElvaney, Tomás P Carroll, Claire Condron, Sanjay H Chotirmall, Martin Clynes, Shane J O'Neill and 1 more

Registry-linked trialOpen access · greenAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07125664 (A Two-center, Randomized, Double-blind, Placebo-controlled Study of Intravenous Plasma-purified Alpha-1 Antitrypsin for Hospitalized Patients With COPD Exacerbations), which is not on this map. Cited by 161 papers.

0numbers the graph read from it
0cells of the map it votes in
161citing papers in PubMed
5.3field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

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.

NCT07125664 phase2not yet recruitingnot on this mapstarted 2025, after this paper: background citation

A Two-center, Randomized, Double-blind, Placebo-controlled Study of Intravenous Plasma-purified Alpha-1 Antitrypsin for Hospitalized Patients With COPD Exacerbations (AECOPD Study)

TypeinterventionalSponsorFondazione IRCCS Policlinico San Matteo di PaviaRan2025 to 2027Enrolled36ConditionsAcute Exacerbation Chronic Obstructive Pulmonary DiseaseArmsalpha1-proteinase inhibitor, produced from the plasma of human donors (Prolastin 1000 mg, powder and solvent for solution for infusion), Placebo
3 · Its place in the literature

Who cites it

161 citing papers in PubMed, 282 citations in OpenAlex.

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  19. Clinical Study Support by Long-Term Stability Studies of AlphaPharmaceuticals (Basel, Switzerland) · 2025
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101 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 1 country.

David A Bergin1Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland.
Emer P Reeves
Paula Meleady
Michael Henry
Oliver J McElvaney
Tomás P Carroll
Claire Condron
Sanjay H Chotirmall
Martin Clynes
Shane J O'Neill
Noel G McElvaney
Beaumont Hospital · IERoyal College of Surgeons in Ireland · IEDublin City University · IE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hereditary deficiency of the protein α-1 antitrypsin (AAT) causes a chronic lung disease in humans that is characterized by excessive mobilization of neutrophils into the lung. However, the reason for the increased neutrophil burden has not been fully elucidated. In this study we have demonstrated using human neutrophils that serum AAT coordinates both CXCR1- and soluble immune complex (sIC) receptor-mediated chemotaxis by divergent pathways. We demonstrated that glycosylated AAT can bind to IL-8 (a ligand for CXCR1) and that AAT-IL-8 complex formation prevented IL-8 interaction with CXCR1. Second, AAT modulated neutrophil chemotaxis in response to sIC by controlling membrane expression of the glycosylphosphatidylinositol-anchored (GPI-anchored) Fc receptor FcγRIIIb. This process was mediated through inhibition of ADAM-17 enzymatic activity. Neutrophils isolated from clinically stable AAT-deficient patients were characterized by low membrane expression of FcγRIIIb and increased chemotaxis in response to IL-8 and sIC. Treatment of AAT-deficient individuals with AAT augmentation therapy resulted in increased AAT binding to IL-8, increased AAT binding to the neutrophil membrane, decreased FcγRIIIb release from the neutrophil membrane, and normalization of chemotaxis. These results provide new insight into the mechanism underlying the effect of AAT augmentation therapy in the pulmonary disease associated with AAT deficiency.

Indexed as

ADAM17 ProteinADAM Proteinsalpha 1-Antitrypsinalpha 1-Antitrypsin DeficiencyAntigen-Antibody ComplexCase-Control StudiesChemotaxis, LeukocyteGPI-Linked ProteinsHumansInterleukin-8In Vitro TechniquesMembrane MicrodomainsMiddle AgedModels, ImmunologicalMutationNeutrophilsADAM17 ProteinADAM17 protein, humanADAM Proteinsalpha 1-AntitrypsinAntigen-Antibody ComplexCXCL8 protein, humanFCGR3B protein, humanGPI-Linked ProteinsInterleukin-8Receptors, IgGReceptors, Interleukin-8ARecombinant Proteins

Identifiers

PMID21060150
PMCPMC2993580
OpenAlexW2162602081

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.