ArticleThe Journal of clinical investigation1991
Neutrophil accumulation in the lung in alpha 1-antitrypsin deficiency. Spontaneous release of leukotriene B4 by alveolar macrophages.
Article in The Journal of clinical investigation, 1991. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis that pooled it.
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Who cites it
68 citing papers in PubMed, 1 synthesis or guideline pooled it, 214 citations in OpenAlex.
- Sputum myeloperoxidase in chronic obstructive pulmonary disease.European journal of medical research · 2014Pooled it
- Anti-PcrV antibody in cystic fibrosis: a novel approach targeting Pseudomonas aeruginosa airway infection.Pediatric pulmonology · 2014Trial
- Inhibition of leukotriene B4-induced CD11B/CD18 (Mac-1) expression by BIIL 284, a new long acting LTB4 receptor antagonist, in patients with rheumatoid arthritis.Annals of the rheumatic diseases · 2004Trial
- Elastic Fibers in the Pathogenesis of Cystic Fibrosis: Mechanisms, Consequences, and Therapeutic Implications.Life (Basel, Switzerland) · 2026Review
- Immunological and homeostatic pathways of alpha -1 antitrypsin: a new therapeutic potential.Frontiers in immunology · 2024Review
- Alpha-defensins inhibit ERK/STAT3 signaling during monocyte-macrophage differentiation and impede macrophage function.Respiratory research · 2023Article
- Neutrophil elastase activates the release of extracellular traps from COPD blood monocyte-derived macrophages.Clinical and translational science · 2023Article
- Impact of Bronchiectasis on COPD Severity and Alpha-1 Antitrypsin Deficiency as a Risk Factor in Individuals with a Heavy Smoking History.Chronic obstructive pulmonary diseases (Miami, Fla.) · 2023Article
- Diagnosis and Management of Cystic Fibrosis Exacerbations.Seminars in respiratory and critical care medicine · 2023Review
- Lung Inflammation in alpha-1-antitrypsin deficient individuals with normal lung function.Respiratory research · 2023Article
- COVID-19 Pathology Sheds Further Light on Balance between Neutrophil Proteases and Their Inhibitors.Biomolecules · 2022Review
- Abnormal neutrophil polarization in chronic obstructive pulmonary disease and how cigarette smoke extracts attract neutrophils.Annals of translational medicine · 2022Article
- C3d Elicits Neutrophil Degranulation and Decreases Endothelial Cell Migration, with Implications for Patients with Alpha-1 Antitrypsin Deficiency.Biomedicines · 2021Article
- Article
- Alpha-1 Antitrypsin Augmentation Inhibits Proteolysis of Neutrophil Membrane Voltage-Gated Proton Channel-1 in Alpha-1 Deficient Individuals.Medicina (Kaunas, Lithuania) · 2021Article
- Gene coexpression networks reveal novel molecular endotypes in alpha-1 antitrypsin deficiency.Thorax · 2021Article
- Exacerbations of Lung Disease in Alpha-1 Antitrypsin Deficiency.Chronic obstructive pulmonary diseases (Miami, Fla.) · 2021Article
- Anti-cytokines as a Strategy in Alpha-1 Antitrypsin Deficiency.Chronic obstructive pulmonary diseases (Miami, Fla.) · 2020Review
- Monocytes and Macrophages in Alpha-1 Antitrypsin Deficiency.International journal of chronic obstructive pulmonary disease · 2020Review
- Alpha 1 Antitrypsin-Deficient Macrophages Have Impaired Efferocytosis of Apoptotic Neutrophils.Frontiers in immunology · 2020Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The emphysema of alpha 1-antitrypsin (alpha 1AT) deficiency is conceptualized to result from insufficient alpha 1AT allowing neutrophil elastase to destroy lung parenchyma. In addition to the deficiency of alpha 1AT in these individuals resulting from mutations in the alpha 1AT gene, it is recognized that, for unknown reasons, there are also increased numbers of neutrophils in their lungs compared with normal individuals. With the knowledge that alveolar macrophages have surface receptors for neutrophil elastase, we hypothesized that the neutrophil accumulation in the lower respiratory tract in alpha 1AT deficiency may result, in part, from release of neutrophil chemotactic activity by alveolar macrophages as they bind uninhibited neutrophil elastase. Consistent with this hypothesis, alpha 1AT-deficient alveolar macrophages spontaneously released nearly threefold more neutrophil chemotactic activity than normal alveolar macrophages. Analysis of alpha 1AT-deficient macrophage supernates by reverse-phase HPLC, molecular sieve chromatography, radioimmunoassay, and absorption with anti-LTB4 antibody revealed that the majority of the chemotactic activity was leukotriene B4 (LTB4), a mediator absent from normal macrophage supernates. Consistent with this hypothesis, incubation of normal macrophages with human neutrophil elastase resulted in the release of the same neutrophil chemotactic mediator. Furthermore, purified human alpha 1AT was able to prevent the neutrophil elastase from stimulating the macrophages to release the chemotactic factor. Together, these findings suggest that the absence of a normal antineutrophil elastase screen in the lower respiratory tract permits free neutrophil elastase to bind to alveolar macrophages, resulting in the release of LTB4, a process which attracts neutrophils to the alveoli of alpha 1AT deficient individuals, thus accelerating the lung destruction that characterizes this disorder.
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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.