Evidence map›Paper›PMID 34572313›Full record

ArticleBiomedicines2021

The FcγRIII Engagement Augments PMA-Stimulated Neutrophil Extracellular Traps (NETs) Formation by Granulocytes Partially via Cross-Talk between Syk-ERK-NF-κB and PKC-ROS Signaling Pathways.

Cheng-Hsun Lu, Ko-Jen Li, Cheng-Han Wu, Chieh-Yu Shen, Yu-Min Kuo, Song-Chou Hsieh, Chia-Li Yu

Open access · goldAbstract read
In one paragraph

Article in Biomedicines, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
0.8field-weighted citation impact, top 30% 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

20 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Review
  3. Alveolar macrophage-neutrophil crosstalk in acute lung injury: mechanisms, feedback loops, and therapeutic opportunities.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Review
  4. PeerJ · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. Neutrophil Extracellular Traps in Atherosclerosis: Research Progress.International journal of molecular sciences · 2025
    Review
  9. Article
  10. Article
  11. Review
  12. Review
  13. Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article
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

7 authors at 2 institutions in 1 country.

Cheng-Hsun LuDepartment of Internal Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan.ORCID 0000-0002-4794-9438
Ko-Jen LiDepartment of Internal Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan.
Cheng-Han WuDepartment of Internal Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan.
Chieh-Yu ShenDepartment of Internal Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan.ORCID 0000-0002-3218-0689
Yu-Min KuoDepartment of Internal Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan.
Song-Chou HsiehDepartment of Internal Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan.
Chia-Li YuDepartment of Internal Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan.ORCID 0000-0003-4988-0400
National Taiwan University · TWNational Taiwan University Hospital · TW

Funding

Ministry of Science and Technology, Taiwan 108-2314-B-002-098Ministry of Science and Technology, Taiwan 109-2314-B-002-234National Taiwan University Hospital Yun-lin Branch NTUHYL.104N004Taiwan Rheumatology Association TRA201602
6 · The paper itself

Abstract

Polymorphonuclear neutrophils (PMNs) are the most abundant white blood cell in the circulation capable of neutrophil extracellular traps (NETs) formation after stimulation. Both NADPH oxidase-dependent and -independent pathways are involved in NET formation. The IgG is the most abundant immunoglobulin in human serum. However, the impact of the circulating IgG on NET formation is totally unexplored. In this study, the all-trans retinoic acid (ATRA)-induced mature granulocytes (dHL-60) were pre-treated with monomeric human IgG, papain-digested Fab fragment, crystallizable IgG Fc portion, rituximab (a human IgG1), or IgG2. The NET formation of the dHL-60 in the presence/absence of phorbol 12-myristate 13-acetate (PMA) stimulation was then measured by the fluorescent area after SYTOX green nucleic acid stain. The intracellular reactive oxygen species (ROS) generation was measured by flow cytometry. Total and phosphorylated Syk, SHP-1, and ERK were detected by immunoblot. We found that human monomeric IgG and its subclasses IgG1 and IgG2 per se induced negligible NET formation of dHL-60, but the FcγRIII engagement by these IgG subclasses and Fc portion augment PMA-stimulated dHL-60 NET formation in a dose-dependent manner. Furthermore, we found that increased Syk and ERK phosphorylation, intracellular ROS generation, and pro-inflammatory cytokines, IL-8 and TNF-α, production could be induced after FcγRIII engagement. Blocking FcγRIII engagement by a specific antibody diminished the augmented NET formation. In conclusion, we discovered that cross-talk between FcγRIII engagement-induced Syk-ERK and PMA-induced PKC signaling pathways augment NET formation of dHL-60 via increased ROS generation and pro-inflammatory cytokines, IL-8 and TNF-α, production.

Indexed as

differentiated HL-60 cellsFcγRIII engagementIgG subclassneutrophil extracellular trapsPAD4polymorphonuclear neutrophilreactive oxygen speciesSyk-ERK signaling pathway

Identifiers

PMID34572313
PMCPMC8472361
OpenAlexW3198809776

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.