Evidence map›Paper›PMID 30154112›Full record

ArticleBlood2018

Charcot-Leyden crystal formation is closely associated with eosinophil extracellular trap cell death.

Shigeharu Ueki, Takahiro Tokunaga, Rossana C N Melo, Hidekazu Saito, Kohei Honda, Mineyo Fukuchi, Yasunori Konno, Masahide Takeda, Yohei Yamamoto, Makoto Hirokawa and 3 more

Open access · greenAbstract read
In one paragraph

Article in Blood, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.

0numbers the graph read from it
0cells of the map it votes in
98citing papers in PubMed
11.4field-weighted citation impact, top 1% 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

98 citing papers in PubMed, 183 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Mucus Plugs and Eosinophilic Inflammation: Expanding the Paradigm to COPD.The journal of allergy and clinical immunology. In practice · 2026
    Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. Review
  13. The immunology of asthma.Nature immunology · 2025
    Review
  14. Article
  15. IgG4-related disease with eosinophil extracellular traps.QJM : monthly journal of the Association of Physicians · 2025
    Article
  16. Article
  17. Eosinophil ETosis and Charcot-Leyden crystals in Kimura disease.The journal of allergy and clinical immunology. Global · 2025
    Article
  18. Treatment of allergic bronchopulmonary aspergillosis with biologics.Chinese medical journal pulmonary and critical care medicine · 2025
    Review
  19. Review
  20. Crowding and in-Cell Crystallization.Sub-cellular biochemistry · 2025
    Review

38 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 5 institutions in 3 countries.

Shigeharu UekiDepartment of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan.ORCID 0000-0002-3537-7735
Takahiro TokunagaDivision of Otorhinolaryngology, Head & Neck Surgery, University of Fukui, Fukui, Japan.
Rossana C N MeloDivision of Allergy and Inflammation, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
Hidekazu SaitoDepartment of Otorhinolaryngology, Head & Neck Surgery, Akita University Hospital, Akita, Japan.
Kohei HondaDepartment of Otorhinolaryngology, Head & Neck Surgery, Akita University Hospital, Akita, Japan.
Mineyo FukuchiDepartment of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan.
Yasunori KonnoDepartment of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan.
Masahide TakedaDepartment of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan.
Yohei YamamotoDepartment of Molecular Pathology and Tumor Pathology, Akita University Graduate School of Medicine, Akita, Japan; and.
Makoto HirokawaDepartment of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan.
Shigeharu FujiedaDivision of Otorhinolaryngology, Head & Neck Surgery, University of Fukui, Fukui, Japan.
Lisa A SpencerDivision of Allergy and Inflammation, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
Peter F WellerDivision of Allergy and Inflammation, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
Akita University · JPBeth Israel Deaconess Medical Center · USAkita University Hospital · JPUniversity of Fukui · JPUniversidade Federal de Juiz de Fora · BR

Funding

Human Eosinophils: Mechanisms of FunctioningR37AI020241 · NIAID · BETH ISRAEL DEACONESS MEDICAL CENTER · PI WELLER, PETER F · 2010 to 2019
$4.5M
Eosinophil functions in allergic gastrointestinal diseasesR01AI121186 · NIAID · UNIVERSITY OF COLORADO DENVER · PI SPENCER, LISA ANN · 2017 to 2021
$2.0M
NIAID NIH HHS R01 AI121186NIAID NIH HHS R37 AI020241
6 · The paper itself

Abstract

Protein crystallization in human tissue rarely occurs. Charcot-Leyden crystals (CLCs) were described in various eosinophilic diseases >150 years ago, but our understanding of CLC formation still remains limited. In this study, we demonstrate that CLCs observed in varied inflamed human tissues are closely associated with eosinophil cell-free granules and nuclear envelope/plasma membrane disintegration with release of filamentous chromatin (extracellular traps), typical morphologies of a regulated pathway of extracellular trap cell death (ETosis). During the process of eosinophil ETosis, eccentrically localized cytoplasmic and perinuclear CLC protein (galectin-10) is homogeneously redistributed in the cytoplasm. Rapid (1-2 minutes) formation of intracytoplasmic CLCs was observed using time-lapse imaging. Plasma membrane rupture enabled the release of both intracellularly formed CLCs and soluble galectin-10 that further contributed to formation of CLCs extracellularly, in parallel with the expulsion of free intact granules and extracellular traps. CLC formation and galectin-10 release were dependent on nicotinamide adenine dinucleotide phosphate oxidase activation. To our knowledge, this is the first demonstration of natural formation of CLCs in association with an active physiological process (ie, ETosis). These results indicate that dynamic changes in intracellular localization and release of galectin-10 contribute to CLC formation in vivo and suggest that CLC/galectin-10 might serve as an indicator of ETosis.

Indexed as

Cell DeathCell MembraneCrystallizationEosinophilsExtracellular TrapsGalectinsHumansInflammationgalectin 10, humanGalectins

Identifiers

PMID30154112
PMCPMC6238188
OpenAlexW2888967065

What OpenQuestion holds

Textmetadata
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.