Evidence map›Paper›PMID 28013195›Full record

ArticleRheumatology (Oxford, England)2017

Nicotine drives neutrophil extracellular traps formation and accelerates collagen-induced arthritis.

Jaejoon Lee, Ayala Luria, Christopher Rhodes, Harini Raghu, Nithya Lingampalli, Orr Sharpe, Balazs Rada, Dong Hyun Sohn, William H Robinson, Jeremy Sokolove

Registry-linked trialOpen access · hybridAbstract read
In one paragraph

Article in Rheumatology (Oxford, England), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04474392 (Sputum Studies of Anti-Citrullinated Protein Antibodies), which is not on this map. Cited by 51 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed, 3 pooled it
6.1field-weighted citation impact, top 3% 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.

NCT04474392 completednot on this mapstarted 2020, after this paper: background citation

Sputum Studies of Anti-Citrullinated Protein Antibodies (ACPA) and Rheumatoid Arthritis (RA) Origins

TypeobservationalSponsorUniversity of Colorado, DenverRan2020 to 2026Enrolled340ConditionsRheumatoid ArthritisArmsN/A (Observational Study)
3 · Its place in the literature

Who cites it

51 citing papers in PubMed, 3 syntheses or guidelines pooled it, 93 citations in OpenAlex.

  1. Pooled it
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  12. [Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024
    Article
  13. The Lung in Rheumatoid Arthritis-Friend or Enemy?International journal of molecular sciences · 2024
    Review
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  15. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 2 countries.

Jaejoon LeeDivision of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA.
Ayala LuriaDivision of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA.
Christopher RhodesDivision of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA.
Harini RaghuDivision of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA.
Nithya LingampalliDivision of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA.
Orr SharpeDivision of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA.
Balazs RadaDepartment of Infectious Diseases, University of Georgia College of Veterinary Medicine, Athens, GA, USA.
Dong Hyun SohnDepartment of Microbiology and Immunology, Pusan National University School of Medicine, Pusan, Korea.
William H RobinsonDivision of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA.
Jeremy SokoloveDivision of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA.
VA Palo Alto Health Care System · USStanford University · USPusan National University · KRUniversity of Georgia · US

Funding

Large-Scale Characterization of Autoantibody Responses in Rheumatoid ArthritisR01AR063676 · NIAMS · STANFORD UNIVERSITY · PI ROBINSON, WILLIAM H · 2013 to 2017
$1.7M
Citrullinated Antigens Bridge Innate and Adaptive Immunity in RAIK2BX001301 · VA · VETERANS ADMIN PALO ALTO HEALTH CARE SYS · PI SOKOLOVE, JEREMY B · 2011 to 2015
–
BLRD VA IK2 BX001301NIAMS NIH HHS R01 AR063676
6 · The paper itself

Abstract

Objectives: The aim was to investigate the effects of nicotine on neutrophil extracellular traps (NETs) formation in current and non-smokers and on a murine model of RA. Methods: We compared spontaneous and phorbol 12-myristate 13-acetate-induced NETosis between current and non-smokers by DNA release binding. Nicotine-induced NETosis from non-smokers was assessed by DNA release binding, NET-specific (myeloperoxidase (MPO)-DNA complex) ELISA and real-time fluorescence microscopy. We also used immunofluorescent staining to detect nicotinic acetylcholine receptors (nAChRs) on neutrophils and performed a functional analysis to assess the role of nAChRs in nicotine-induced NETosis. Finally, we investigated the effects of systemic nicotine exposure on arthritis severity and NETosis in the CIA mouse model. Results: Neutrophils derived from current smokers displayed elevated levels of spontaneous and phorbol 12-myristate 13-acetate-induced NETosis. Nicotine induced dose-dependent NETosis in ex vivo neutrophils from healthy non-smokers, and co-incubation with ACPA-immune complexes or TNF-α facilitated a synergistic effect on NETosis. Real-time fluorescence microscopy revealed robust formation of NET-like structures in nicotine-exposed neutrophils. Immunofluorescent staining demonstrated the presence of the α7 subunit of the nAChR on neutrophils. Stimulation of neutrophils with an α7-specific nAChR agonist induced NETosis, whereas pretreatment with an nAChR antagonist attenuated nicotine-induced NETosis. Nicotine administration to mice with CIA exacerbated inflammatory arthritis, with higher plasma levels of NET-associated MPO-DNA complex. Conclusion: We demonstrate that nicotine is a potent inducer of NETosis, which may play an important role in accelerating arthritis in the CIA model. This study generates awareness of and the mechanisms by which nicotine-containing products, including e-cigarettes, may have deleterious effects on patients with RA.

Indexed as

AnimalsArthritis, ExperimentalArthritis, RheumatoidCartilageDose-Response Relationship, DrugElectronic Nicotine Delivery SystemsEnzyme-Linked Immunosorbent AssayExtracellular TrapsHumansInfusions, SubcutaneousMaleMice, Inbred DBANeutrophilsNicotineNicotinic AgonistsPeroxidaseNicotineNicotinic AgonistsPeroxidaseTetradecanoylphorbol Acetateanimal modelcollagen-induced arthritisneutrophil extracellular trapsnicotinerheumatoid arthritis

Identifiers

PMID28013195
PMCPMC5850711
OpenAlexW2566616762

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.