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Charcot-Leyden crystal protein/galectin-10 interacts with cationic ribonucleases and is required for eosinophil granulogenesis.

Authors
  • Grozdanovic, Milica M1
  • Doyle, Christine B1
  • Liu, Li1
  • Maybruck, Brian T1
  • Kwatia, Mark A1
  • Thiyagarajan, Nethaji2
  • Acharya, K Ravi2
  • Ackerman, Steven J3
  • 1 Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, Ill.
  • 2 Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom. , (United Kingdom)
  • 3 Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, Ill. Electronic address: [email protected]
Type
Published Article
Journal
The Journal of allergy and clinical immunology
Publication Date
Aug 01, 2020
Volume
146
Issue
2
Identifiers
DOI: 10.1016/j.jaci.2020.01.013
PMID: 31982451
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The human eosinophil Charcot-Leyden crystal (CLC) protein is a member of the Galectin superfamily and is also known as galectin-10 (Gal-10). CLC/Gal-10 forms the distinctive hexagonal bipyramidal crystals that are considered hallmarks of eosinophil participation in allergic responses and related inflammatory reactions; however, the glycan-containing ligands of CLC/Gal-10, its cellular function(s), and its role(s) in allergic diseases are unknown. We sought to determine the binding partners of CLC/Gal-10 and elucidate its role in eosinophil biology. Intracellular binding partners were determined by ligand blotting with CLC/Gal-10, followed by coimmunoprecipitation and coaffinity purifications. The role of CLC/Gal-10 in eosinophil function was determined by using enzyme activity assays, confocal microscopy, and short hairpin RNA knockout of CLC/Gal-10 expression in human CD34+ cord blood hematopoietic progenitors differentiated to eosinophils. CLC/Gal-10 interacts with both human eosinophil granule cationic ribonucleases (RNases), namely, eosinophil-derived neurotoxin (RNS2) and eosinophil cationic protein (RNS3), and with murine eosinophil-associated RNases. The interaction is independent of glycosylation and is not inhibitory toward endoRNase activity. Activation of eosinophils with INF-γ induces the rapid colocalization of CLC/Gal-10 with eosinophil-derived neurotoxin/RNS2 and CD63. Short hairpin RNA knockdown of CLC/Gal-10 in human cord blood-derived CD34+ progenitor cells impairs eosinophil granulogenesis. CLC/Gal-10 functions as a carrier for the sequestration and vesicular transport of the potent eosinophil granule cationic RNases during both differentiation and degranulation, enabling their intracellular packaging and extracellular functions in allergic inflammation. Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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