Galectin-10 is a member of the lectin family and one of the most abundant cytoplasmic proteins in human eosinophils. Except for some myeloid leukemia cells, basophils, and minor T cell populations, galectin-10 is exclusively present in eosinophils in the human body. Galectin-10 forms Charcot–Leyden crystals, which are observed in various eosinophilic diseases. Accumulating studies have indicated that galectin-10 acts as a new biomarker for disease activity, diagnosis, and treatment effectiveness in asthma, eosinophilic esophagitis, rhinitis, sinusitis, atopic dermatitis, and eosinophilic granulomatosis with polyangiitis. The extracellular release of galectin-10 is not mediated through conventional secretory processes (piecemeal degranulation or exocytosis), but rather by extracellular trap cell death (ETosis), which is an active cell death program. Eosinophils undergoing ETosis rapidly disintegrate their plasma membranes to release the majority of galectin-10. Therefore, elevated galectin-10 levels in serum and tissue suggest a high degree of eosinophil ETosis. To date, several studies have shown that galectin-10/Charcot–Leyden crystals are more than just markers for eosinophilic inflammation, but play functional roles in immunity. In this review, we focus on the close relationship between eosinophils and galectin-10, highlighting this protein as a potential new biomarker in eosinophilic diseases.

Cytolytic ETosis is a type of programmed cell death that is distinct from apoptosis and necrosis and plays a major role in the innate immune system and disease progression. Through the process of ETosis, cells release their chromatin with diverse antimicrobial proteins into the extracellular milieu, forming extracellular traps (ETs). Although ETosis has been reported in several leukocyte types, few studies have compared ETosis and the component proteins of ETs in leukocytes. The aim of this study was to better understand the characteristics of eosinophil ETosis (EETosis) compared with other leukocytes. We isolated human blood eosinophils, neutrophils, basophils, monocytes, and lymphocytes and stimulated them with known ETosis inducers: the protein kinase C activator PMA and calcium ionophore A23187. Both stimuli induced eosinophil cell death and ET release after 180 minutes of stimulation in a nicotinamide adenine dinucleotide phosphate oxidase–dependent manner. PMA also induced nicotinamide adenine dinucleotide phosphate oxidase–dependent ETosis in neutrophils, whereas little or no significant ETosis was observed in basophils, monocytes, or lymphocytes at 180 minutes. Mass spectrometry–based proteomic analysis of eosinophil- and neutrophil-derived ETs identified 997 and 1,415 proteins, respectively. Among the physiological stimuli tested, immobilized IgA and IgG induced EETosis. CCL11 (C-C motif chemokine ligand 11) and IL-5 were weak inducers of EETosis, but costimulation significantly induced rapid EETosis. Under high serum or albumin conditions, costimulation with CCL11 and IL-5 paradoxically prolonged cell survival by preventing spontaneous apoptosis. This study provides an in-depth characterization of EETosis and highlights the precise regulation of eosinophil survival and cell death pathways.

Uncontrolled airway mucus is associated with diverse diseases. We hypothesized that the physical characteristics of infiltrating granulocytes themselves affect the clinical properties of mucus. Surgically obtained nasal mucus from patients with eosinophilic chronic rhinosinusitis (ECRS) and neutrophil-dominant non-eosinophilic chronic rhinosinusitis (non-ECRS) was assessed in terms of computed tomography (CT) density, viscosity, water content, wettability, and granulocyte-specific proteins. In an observational study, we found that nasal mucus from patients with ECRS had significantly higher CT density, viscosity, dry weight, and hydrophobicity than mucus from patients with non-ECRS. The levels of eosinophil-specific proteins in nasal mucus correlated with its physical properties. When isolated human eosinophils and neutrophils were stimulated to induce extracellular traps followed by aggregate formation, we found that cell aggregates showed physical and pathological findings that closely resembled mucus. Co-treatment with heparin (which slenderizes the structure of eosinophil extracellular traps) and DNase efficiently induced a reduction in the viscosity and hydrophobicity of both eosinophil aggregates and eosinophilic mucus. The present study highlights the pathogenesis of mucus stasis in infiltrated granulocyte aggregates from a new perspective. The combination of DNase and heparin might be a novel therapeutic modality against pathologic viscous eosinophilic mucus. One Sentence Summary: Intraluminal accumulation and activation of eosinophils contribute to the clinical properties of airway mucus and may serve as a therapeutic target.