Lactose and Galactose Promote the Crystallization of Human Galectin-10

Abstract

Galectin-10 (Gal-10) forms Charcot–Leyden crystals (CLCs), which play a key role in the symptoms of asthma and allergies and some other diseases. Gal-10 has a carbohydrate-binding site; however, neither the Gal-10 dimer nor the CLCs can bind sugars. To investigate the monomer–dimer equilibrium of Gal-10, high-performance size-exclusion chromatography (SEC) was employed to separate serial dilutions of Gal-10 with and without carbohydrates. We found that both the dimerization and crystallization of Gal-10 were promoted by lactose/galactose binding. A peak position shift for the monomer was observed after treatment with either lactose or galactose, implying that the polarity of the monomer was reduced by lactose/galactose binding. Further experiments indicated that alkaline conditions of pH 8.8 mimicked the lactose/galactose-binding environment, and the time interval between monomers and dimers in the chromatogram decreased from 0.8 min to 0.4 min. Subsequently, the electrostatic potential of the Gal-10 monomers was computed. After lactose/galactose binding, the top side of the monomer shifted from negatively charged to electrically neutral, allowing it to interact with the carbohydrate-binding site of the opposing subunit during dimerization. Since lactose/galactose promotes the crystallization of Gal-10, our findings implied that dairy-free diets (free of lactose/galactose) might be beneficial to patients with CLC-related diseases.

Gut microbiome-immune interactions and their role in rheumatoid arthritis development

“…Lactosecat pathway: lactose and galactose degradation I also showed predictable power demonstrating negative association with the most abundant in RA Lachnospiraceae and positively associating with the most abundant in Control group Oscillospiraceae , which could be explained by the capacity of lactose and galactose to induce the production of Galectine-10 ( Fu et al, 2023 ). The latter is related to eosinophilic diseases ( Tomizawa et al, 2022 ) and may contribute to autoimmune disorders as well according to our findings.…”

The Role of Galectins in Asthma Pathophysiology: A Comprehensive Review

“…Nevertheless, the administration of CLCs in mice can induce monocyte/macrophages, dendritic cells, and neutrophils proliferation via TNF-α, IL-1β, and IL-6 production [43]. Interestingly, while molecules like lactose or galactose can induce the development of CLCs through an electrostatic potential shift during Gal-10 dimerization [44], Glutathione appears to inhibit the formation of CLCs in animal models, binding the CRD of CLCs and preventing Gal-10 crystallization [45]. However, apart from its release after crystallization, Gal-10 can also form eosinophil extracellular traps (EETs) along with histone-rich DNA and other cytoplasmic proteins from secondary granules, being secreted by active eosinophils or after their cytolysis (ETosis) [84,85].…”