Evidence map›Paper›PMID 36719377›Full record

ArticleThe Journal of clinical investigation2023

Neutrophil CEACAM1 determines susceptibility to NETosis by regulating the S1PR2/S1PR3 axis in liver transplantation.

Hirofumi Hirao, Hidenobu Kojima, Kenneth J Dery, Kojiro Nakamura, Kentaro Kadono, Yuan Zhai, Douglas G Farmer, Fady M Kaldas, Jerzy W Kupiec-Weglinski

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

Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
7.7field-weighted citation impact, top 2% 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

41 citing papers in PubMed, 47 citations in OpenAlex.

  1. Review
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  14. It's a Trap!-Potential of Cathepsins in NET Formation.International journal of molecular sciences · 2025
    Review
  15. Article
  16. Article
  17. Article
  18. Mouse orthotopic liver transplantation: Challenges, achievements, and applications.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2025
    Review
  19. Optimizing the mouse orthotopic liver transplantation model: Learning curve, technical enhancements, and keys to success.Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society · 2025
    Article
  20. Review
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

9 authors at 3 institutions in 2 countries.

Hirofumi HiraoDumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Hidenobu KojimaDumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Kenneth J DeryDumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Kojiro NakamuraDumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Kentaro KadonoDumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Yuan ZhaiDumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Douglas G FarmerDumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Fady M KaldasDumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Jerzy W Kupiec-WeglinskiDumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
UCLA Health · USKyoto University · JPUniversity of California, Los Angeles · US

Funding

Regulation of Innate Immune Responses by Alloimmunity in Liver Ischemia-Reperfusion InjuryP01AI120944 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ELAINE F REED · 2017 to 2026
$20.0M
NRF2 - SIRT1 SIGNALING AXIS IN LIVER TRANSPLANT REJUVENATIONR01DK062357 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KUPIEC-WEGLINSKI, JERZY W · 2003 to 2025
$8.4M
Tim Costimulation in Liver Transplant Ischemia InjuryR01DK102110 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KUPIEC-WEGLINSKI, JERZY W · 2015 to 2019
$1.7M
TIM-3 Negative Costimulation Signaling at the Innate-Adaptive Immune interface in Liver Transplant Ischemia-Reperfusion InjuryR01DK107533 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KUPIEC-WEGLINSKI, JERZY W · 2016 to 2020
$1.7M
NIAID NIH HHS P01 AI120944NIDDK NIH HHS R01 DK062357NIDDK NIH HHS R01 DK102110NIDDK NIH HHS R01 DK107533
6 · The paper itself

Abstract

Neutrophils, the largest innate immune cell population in humans, are the primary proinflammatory sentinel in the ischemia-reperfusion injury (IRI) mechanism in orthotopic liver transplantation (OLT). Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1, CC1, or CD66a) is essential in neutrophil activation and serves as a checkpoint regulator of innate immune-driven IRI cascade in OLT. Although CC1 alternative splicing generates two functionally distinct short and long cytoplasmic isoforms, their role in neutrophil activation remains unknown. Here, we undertook molecular and functional studies to interrogate the significance of neutrophil CC1 signaling in mouse and human OLT recipients. In the experimental arm, we employed a mouse OLT model to document that ablation of recipient-derived neutrophil CC1-long (CC1-L) isotype aggravated hepatic IRI by promoting neutrophil extracellular traps (NETs). Notably, by regulating the S1P-S1PR2/S1PR3 axis, neutrophil CC1-L determined susceptibility to NET formation via autophagy signaling. In the clinical arm, liver grafts from 55 transplant patients selectively enriched for neutrophil CC1-L showed relative resistance to ischemia-reperfusion (IR) stress/tissue damage, improved hepatocellular function, and clinical outcomes. In conclusion, despite neutrophils being considered a principal villain in peritransplant tissue injury, their CC1-L isoform may serve as a regulator of IR stress resistance/NETosis in human and mouse OLT recipients.

Indexed as

Liver TransplantationReperfusion InjuryAnimalsAntigens, CDCarcinoembryonic AntigenCell Adhesion MoleculesHumansLiverMiceNeutrophilsSphingosine-1-Phosphate ReceptorsTranscription FactorsAntigens, CDCarcinoembryonic AntigenCD66 antigensCeacam1 protein, mouseCell Adhesion MoleculesS1PR2 protein, humanS1pr3 protein, mouseSphingosine-1-Phosphate ReceptorsTranscription FactorsHypoxiaNeutrophilsOrgan transplantationTransplantation

Identifiers

PMID36719377
PMCPMC9888387
OpenAlexW4318667887

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.