Evidence map›Paper›PMID 39242155›Full record

ArticleLife science alliance2024

Mast cell extracellular trap formation underlies vascular and neural injury and hyperalgesia in sickle cell disease.

Donovan A Argueta, Huy Tran, Yugal Goel, Aithanh Nguyen, Julia Nguyen, Stacy B Kiven, Chunsheng Chen, Fuad Abdulla, Gregory M Vercellotti, John D Belcher and 1 more

Abstract read
In one paragraph

Article in Life science alliance, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
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

6 citing papers in PubMed.

  1. Review
  2. Mast Cells in the Developing Brain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026
    Review
  3. Article
  4. Article
  5. Article
  6. 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

11 authors.

Donovan A ArguetaDivision of Hematology/Oncology, Department of Medicine, University of California, Irvine, Irvine, CA, USA.ORCID 0000-0002-8234-141X
Huy TranDivision of Hematology, Oncology, and Transplantation, School of Medicine, University of Minnesota, Twin Cities, Minneapolis, MN, USA.
Yugal GoelDivision of Hematology/Oncology, Department of Medicine, University of California, Irvine, Irvine, CA, USA.ORCID 0000-0002-1224-9271
Aithanh NguyenDivision of Hematology, Oncology, and Transplantation, School of Medicine, University of Minnesota, Twin Cities, Minneapolis, MN, USA.
Julia NguyenDivision of Hematology, Oncology, and Transplantation, School of Medicine, University of Minnesota, Twin Cities, Minneapolis, MN, USA.
Stacy B KivenDivision of Hematology/Oncology, Department of Medicine, University of California, Irvine, Irvine, CA, USA.ORCID 0000-0003-3681-309X
Chunsheng ChenDivision of Hematology, Oncology, and Transplantation, School of Medicine, University of Minnesota, Twin Cities, Minneapolis, MN, USA.
Fuad AbdullaDivision of Hematology, Oncology, and Transplantation, School of Medicine, University of Minnesota, Twin Cities, Minneapolis, MN, USA.
Gregory M VercellottiDivision of Hematology, Oncology, and Transplantation, School of Medicine, University of Minnesota, Twin Cities, Minneapolis, MN, USA.ORCID 0000-0003-1324-0831
John D BelcherDivision of Hematology, Oncology, and Transplantation, School of Medicine, University of Minnesota, Twin Cities, Minneapolis, MN, USA.ORCID 0000-0001-5536-2752
Kalpna GuptaDivision of Hematology/Oncology, Department of Medicine, University of California, Irvine, Irvine, CA, USA kalpnag@hs.uci.edu.ORCID 0000-0001-9381-9979

Funding

Targeting p38/JNK MAPK to ameliorate cisplatin-induced adverse sequelae on the nervous systemR01CA263806 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI BOTA, DANIELA ANNENELIE, GUPTA, KALPNA · 2021 to 2025
$3.4M
Targeting mechanisms contributing to vascular dysfunction and pain in sickle cell diseaseR01HL147562 · NHLBI · UNIVERSITY OF CALIFORNIA-IRVINE · PI GUPTA, KALPNA · 2019 to 2022
$3.4M
Treating pain in sickle cell disease by means of focused ultrasound neuromodulationU18EB029354 · NIBIB · CARNEGIE-MELLON UNIVERSITY · PI HE, BIN · 2019 to 2019
$2.0M
Nutrition-based interventions to ameliorate pain in sickle cell diseaseK99AT012494 · NCCIH · UNIVERSITY OF CALIFORNIA-IRVINE · PI ARGUETA, DONOVAN ALEXANDER · 2024 to 2025
$241k
NCCIH NIH HHS K99 AT012494NCI NIH HHS R01 CA263806NHLBI NIH HHS R01 HL147562NIBIB NIH HHS U18 EB029354
6 · The paper itself

Abstract

Sickle cell disease (SCD) is the most common inherited monogenetic disorder. Chronic and acute pain are hallmark features of SCD involving neural and vascular injury and inflammation. Mast cells reside in the vicinity of nerve fibers and vasculature, but how they influence these structures remains unknown. We therefore examined the mechanism of mast cell activation in a sickle microenvironment replete with cell-free heme and inflammation. Mast cells exposed to this environment showed an explosion of nuclear contents with the release of citrullinated histones, suggestive of mast cell extracellular trap (MCET) release. MCETs interacted directly with the vasculature and nerve fibers, a cause of vascular and neural injury in sickle cell mice. MCET formation was dependent upon peptidylarginine deiminase 4 (PAD4). Inhibition of PAD4 ameliorated vasoocclusion, chronic and acute hyperalgesia, and inflammation in sickle mice. PAD4 activation may also underlie neutrophil trap formation in SCD, thus providing a novel target to treat the sequelae of vascular and neural injury in SCD.

Indexed as

Anemia, Sickle CellExtracellular TrapsHyperalgesiaMast CellsProtein-Arginine Deiminase Type 4AnimalsDisease Models, AnimalHumansInflammationMaleMiceMice, Inbred C57BLNeutrophilspeptidylarginine deiminase 4, mouseProtein-Arginine Deiminase Type 4

Identifiers

PMID39242155
PMCPMC11381676

What OpenQuestion holds

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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 OpenQuestion graph.