Evidence map›Paper›PMID 36068572›Full record

ArticleRespiratory research2022

Cigarette smoke exposed airway epithelial cell-derived EVs promote pro-inflammatory macrophage activation in alpha-1 antitrypsin deficiency.

Nazli Khodayari, Regina Oshins, Borna Mehrad, Jorge E Lascano, Xiao Qiang, Jesse R West, L Shannon Holliday, Jungnam Lee, Gayle Wiesemann, Soroush Eydgahi and 1 more

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Respiratory research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
1.3field-weighted citation impact, top 21% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. The Impact of Environmental Pollution and Climate Change on Allergic Rhinitis and Lung Diseases.World journal of otorhinolaryngology - head and neck surgery · 2026
    Review
  4. Review
  5. Review
  6. Review
  7. Article
  8. Extracellular vesicles and COPD: foe or friend?Journal of nanobiotechnology · 2023
    Review
  9. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 1 institution in 1 country.

Nazli KhodayariDivision of Pulmonary, Critical Care, and Sleep Medicine, College of Medicine, University of Florida, 1600 SW Archer Rd Rm M453A, Gainesville, FL, 32610, USA. Nazli.khodayari@medicine.ufl.edu.
Regina OshinsDivision of Pulmonary, Critical Care, and Sleep Medicine, College of Medicine, University of Florida, 1600 SW Archer Rd Rm M453A, Gainesville, FL, 32610, USA.
Borna MehradDivision of Pulmonary, Critical Care, and Sleep Medicine, College of Medicine, University of Florida, 1600 SW Archer Rd Rm M453A, Gainesville, FL, 32610, USA.
Jorge E LascanoDivision of Pulmonary, Critical Care, and Sleep Medicine, College of Medicine, University of Florida, 1600 SW Archer Rd Rm M453A, Gainesville, FL, 32610, USA.
Xiao QiangMilliporeSigma, Burlington, MO, USA.
Jesse R WestDivision of Pulmonary, Critical Care, and Sleep Medicine, College of Medicine, University of Florida, 1600 SW Archer Rd Rm M453A, Gainesville, FL, 32610, USA.
L Shannon HollidayDepartment of Orthodontics, College of Dentistry, University of Florida, Gainesville, FL, USA.
Jungnam LeeDivision of Pulmonary, Critical Care, and Sleep Medicine, College of Medicine, University of Florida, 1600 SW Archer Rd Rm M453A, Gainesville, FL, 32610, USA.
Gayle WiesemannCollege of Medicine, University of Florida, Gainesville, FL, USA.
Soroush EydgahiDivision of Pulmonary, Critical Care, and Sleep Medicine, College of Medicine, University of Florida, 1600 SW Archer Rd Rm M453A, Gainesville, FL, 32610, USA.
Mark BrantlyDivision of Pulmonary, Critical Care, and Sleep Medicine, College of Medicine, University of Florida, 1600 SW Archer Rd Rm M453A, Gainesville, FL, 32610, USA.
University of Florida · US

Funding

Multiscale modeling of the role of heme during invasive pulmonary aspergillosisR01AI135128 · NIAID · UNIVERSITY OF FLORIDA · PI REINHARD LAUBENBACHER, Borna Mehrad · 2018 to 2026
$4.9M
Modular design of multiscale models, with an application to the innate immune response to fungal respiratory pathogens.U01EB024501 · NIBIB · UNIVERSITY OF FLORIDA · PI LAUBENBACHER, REINHARD, MEHRAD, BORNA · 2017 to 2020
$2.9M
Alpha-1 Foundation F007320NIBIB NIH HHS U01 EB024501
6 · The paper itself

Abstract

backgroundAlpha-1 antitrypsin deficiency (AATD) is a genetic disorder most commonly secondary to a single mutation in the SERPINA1 gene (PI*Z) that causes misfolding and accumulation of alpha-1 antitrypsin (AAT) in hepatocytes and mononuclear phagocytes which reduces plasma AAT and creates a toxic gain of function. This toxic gain of function promotes a pro-inflammatory phenotype in macrophages that contributes to lung inflammation and early-onset COPD, especially in individuals who smoke cigarettes. The aim of this study is to determine the role of cigarette exposed AATD macrophages and bronchial epithelial cells in AATD-mediated lung inflammation.

methodsPeripheral blood mononuclear cells from AATD and healthy individuals were differentiated into alveolar-like macrophages and exposed to air or cigarette smoke while in culture. Macrophage endoplasmic reticulum stress was quantified and secreted cytokines were measured using qPCR and cytokine ELISAs. To determine whether there is "cross talk" between epithelial cells and macrophages, macrophages were exposed to extracellular vesicles released by airway epithelial cells exposed to cigarette smoke and their inflammatory response was determined.

resultsAATD macrophages spontaneously produce several-fold more pro-inflammatory cytokines as compared to normal macrophages. AATD macrophages have an enhanced inflammatory response when exposed to cigarette smoke-induced extracellular vesicles (EVs) released from airway epithelial cells. Cigarette smoke-induced EVs induce expression of GM-CSF and IL-8 in AATD macrophages but have no effect on normal macrophages. Release of AAT polymers, potent neutrophil chemo attractants, were also increased from AATD macrophages after exposure to cigarette smoke-induced EVs.

conclusionsThe expression of mutated AAT confers an inflammatory phenotype in AATD macrophages which disposes them to an exaggerated inflammatory response to cigarette smoke-induced EVs, and thus could contribute to progressive lung inflammation and damage in AATD individuals.

Indexed as

alpha 1-Antitrypsin DeficiencyCigarette SmokingExtracellular VesiclesPneumoniaPulmonary Disease, Chronic Obstructivealpha 1-AntitrypsinCytokinesEpithelial CellsLeukocytes, MononuclearMacrophage ActivationNicotianaalpha 1-AntitrypsinCytokinesAlpha-1 antitrypsinCigarette smokeExtracellular vesiclesLung diseaseMacrophages

Identifiers

PMID36068572
PMCPMC9446525
OpenAlexW4294808270

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.