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

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-10containing extracellular vesicles are also released during ETosis. Mice models indicated that CLCs could be a novel therapeutic target for Th2-type airway inflammation.

Nonimmunoglobulin Crystal-Storing Histiocytosis (CSH): Case Report and Literature Review

“…Charcot–Leyden crystals have hexagonal and bipyramidal forms [ 11 ]. They are compounds of galectin-10 (Gal-10), a member of the family of S-type lectin proteins [ 12 ]. Gal-10 is a major constituent of eosinophils, estimated to be around 7–10% of total cellular proteins.…”

“…Gal-10 is a major constituent of eosinophils, estimated to be around 7–10% of total cellular proteins. A higher percentage is usually a sign of eosinophilic inflammation [ 12 ]. This protein is insoluble at neutral pH, remarkably resistant to various enzymes, and exhibits a tendency to form noncovalent aggregates [ 12 ].…”

Protein phase separation and determinants of in cell crystallization

“…Further, in cellulo crystallization has also been associated with several diseases like cataract, hemoglobin C diseases, formation of Charcot‐Leyden crystals (CLCs), Reinke's crystals or mitochondrial myopathies, and more recently in cellulo crystallization was observed as a result of heterologous overexpression of genes in cell lines of bacteria, insect cells, yeast, CHO (Chinese hamster ovary) or HEK (human embryonic kidney) cells . Mostly, these protein crystals were located in different organelles (mitochondria, peroxisomes, lysosomes, or endoplasmic reticulum), as shown in Table but sometimes also within the cytosol or even in the nucleus, as shown in Figure and Table .…”

“…In the context of human diseases called “crystallopathies”, it has been demonstrated that Galectin 10 is the major component of CLCs which plays an essential role in the pathogenicity of several diseases . A recent study solved the Galectin 10 structure using CLCs from patients with rhinosinusitis and asthma.…”

Charcot-Leyden Crystal Protein in Nasal Secretions of Patients with Nonallergic Rhinitis with Eosinophilia Syndrome

“…Charcot-Leyden crystal (CLC) protein, also known as galectin-10, is the 10th member of the galectin superfamily of S-type lectins. CLC protein is abundant in the cytoplasm of eosinophils [7, 8] and can be crystallized during cytolytic extracellular trap cell death [9-11], before being released by activated eosinophils. CLC protein has been described for over 150 years in tissue, body fluids, and secretions of patients with a variety of eosinophilic lesions, including asthma [12], AR [13, 14], chronic rhinosinusitis (CRS) [15, 16], and other eosinophil-associated diseases [17], and regarded as a hallmark of eosinophilic inflammation.…”