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Charcot-Leyden Crystals in Eosinophilic Inflammation: Active Cytolysis Leads to Crystal Formation

  • Shigeharu UekiEmail author
  • Yui Miyabe
  • Yohei Yamamoto
  • Mineyo Fukuchi
  • Makoto Hirokawa
  • Lisa A. Spencer
  • Peter F. Weller
Otitis (DP Skoner, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Otitis

Abstract

Purpose of Review

Charcot-Leyden crystals (CLCs), slender bipyramidal hexagonal crystals, were first described by Jean-Martin Charcot in 1853, predating Paul Ehrlich’s “discovery” of eosinophils by 26 years. To date, CLCs are known as a classical hallmark of eosinophilic inflammation. CLC protein expresses palmitate cleaving lysophospholipase activity and is a member of the family of S-type lectins, galectin-10. We summarize current knowledge regarding the pathological observations of CLCs and their mechanism of generation focusing on eosinophil cell death.

Recent Findings

The presence of CLCs in vivo has been consistently associated with lytic eosinophils. Recent evidence revealed that cytolysis represents the occurrence of extracellular trap cell death (ETosis), an active non-apoptotic cell death process releasing filamentous chromatin structure. Galectin-10 is a predominant protein present within the cytoplasm of eosinophils but not stored in secretory granules. Activated eosinophils undergo ETosis and loss of galectin-10 cytoplasmic localization results in intracellular CLC formation. Free galectin-10 released following plasma membrane disintegration forms extracellular CLCs. Of interest, galectin-10-containing extracellular vesicles are also released during ETosis. Mice models indicated that CLCs could be a novel therapeutic target for Th2-type airway inflammation.

Summary

The concept of ETosis, which represents a major fate of activated eosinophils, expands our current understanding by which cytoplasmic galectin-10 is crystalized/externalized. Besides CLCs and free galectin-10, cell-free granules, extracellular chromatin traps, extracellular vesicles, and other alarmins, all released through the process of ETosis, have novel implications in various eosinophilic disorders.

Keywords

Charcot-Leyden crystal Degranulation Extracellular traps Eosinophils Galectin-10 

Abbreviations

CLC

Charcot-Leyden crystal

CRSwNP

Chronic rhinosinusitis with nasal polyps

EETosis

Eosinophil extracellular trap cell death

ETosis

Extracellular trap cell death

ETs

Extracellular traps, DNA traps

EV

Extracellular vesicle

NETosis

Neutrophil extracellular trap cell death

Notes

Acknowledgments

The authors are grateful to Satomi Misawa for outstanding assistance in drawing the figure.

Funding Information

This study was funded in part by a Research Grant on Allergic Disease and Immunology from the Japan Agency for Medical Research and Development (JP19ek0410055), Charitable Trust Laboratory Medicine Research Foundation of Japan, Japanese Society of Laboratory Medicine Fund for Promotion of Scientific Research, and JSPS KAKENHI 15KK0329, 16K08926 (SU), NIH R37AI020241 (PFW), and NIH R01AI121186 (LAS).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019
corrected publication 2019

Authors and Affiliations

  • Shigeharu Ueki
    • 1
    Email author
  • Yui Miyabe
    • 1
    • 2
  • Yohei Yamamoto
    • 3
  • Mineyo Fukuchi
    • 1
  • Makoto Hirokawa
    • 1
  • Lisa A. Spencer
    • 4
  • Peter F. Weller
    • 5
  1. 1.Department of General Internal Medicine and Clinical Laboratory MedicineAkita University Graduate School of MedicineAkitaJapan
  2. 2.Department of Otorhinolaryngology, Head & Neck SurgeryAkita University HospitalAkitaJapan
  3. 3.Department of Molecular Pathology and Tumor PathologyAkita University Graduate School of MedicineAkitaJapan
  4. 4.Department of PediatricsUniversity of Colorado School of MedicineDenverUSA
  5. 5.Divisions of Allergy and Inflammation and Infectious Diseases, Department of Medicine, Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonUSA

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