Charcot-Leyden crystals: solving an enigma

Abstract

In this issue of Blood, Ueki et al elegantly demonstrate the active formation of Charcot-Leyden crystals (CLCs) during eosinophil cytolysis. After confirming the association of CLC deposition with eosinophilic inflammation and eosinophil plasma membrane disruption in tissue sections by light and electron microscopy, Ueki et al used a combination of sophisticated imaging techniques, including immunofluorescent time-lapse photography, to follow the course of CLC formation in vitro in response to a variety of stimuli that induce eosinophil extracellular trap death (EETosis). The association of CLC with the disintegration of eosinophils was proposed as early as the 1940s, and agents, such as Aerosol MA, which disrupt the integrity of eosinophils, were subsequently shown to promote CLC formation in vitro in the surrounding media. Ueki et al provide the first definitive evidence that CLC formation is energy-dependent and closely tied to the process of EETosis (see figure).

EETosis mediates galectin-10 crystallization. The graphic shows the temporal course of galectin-10 crystallization in tissues. During stimuli-elicited EETosis, loss of regulated intracellular localization of galectin-10 occasionally causes galectin-10 crystallization in the cytoplasm before cell lysis. Galectin-10 is released by plasma membrane disintegration, which may result in extracellular crystallization by increasing local concentrations. Some galectin-10 is also budded from the plasma membrane within enveloped EVs. Thus, FEG, ETs, and galectin-10–containing EV were associated with varied sizes of CLC. Tissue macrophages can also take up galectin-10 and/or small CLC. ET, extracellular trap; EV, extracellular vesicle; FEG, free extracellular granule. See supplemental Figure 8 in the article by Ueki et al that begins on page 2183.