Charcot-Leyden Crystals in Eosinophilic Inflammation: Active Cytolysis Leads to Crystal Formation
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.
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.
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.
KeywordsCharcot-Leyden crystal Degranulation Extracellular traps Eosinophils Galectin-10
Chronic rhinosinusitis with nasal polyps
Eosinophil extracellular trap cell death
Extracellular trap cell death
Extracellular traps, DNA traps
Neutrophil extracellular trap cell death
The authors are grateful to Satomi Misawa for outstanding assistance in drawing the figure.
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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