Galectin-9 mediates neutrophil capture and adhesion in a CD44 and β2 integrin-dependent manner.



Iqbal, Asif J ORCID: 0000-0002-3224-3651, Krautter, Franziska, Blacksell, Isobel A, Wright, Rachael D ORCID: 0000-0002-7606-2297, Austin-Williams, Shani N, Voisin, Mathieu-Benoit, Hussain, Mohammed T, Law, Hannah L, Niki, Toshiro, Hirashima, Mitsuomi
et al (show 6 more authors) (2022) Galectin-9 mediates neutrophil capture and adhesion in a CD44 and β2 integrin-dependent manner. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 36 (1). e22065 - ?.

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Abstract

Neutrophil trafficking is a key component of the inflammatory response. Here, we have investigated the role of the immunomodulatory lectin Galectin-9 (Gal-9) on neutrophil recruitment. Our data indicate that Gal-9 is upregulated in the inflamed vasculature of RA synovial biopsies and report the release of Gal-9 into the extracellular environment following endothelial cell activation. siRNA knockdown of endothelial Gal-9 resulted in reduced neutrophil adhesion and neutrophil recruitment was significantly reduced in Gal-9 knockout mice in a model of zymosan-induced peritonitis. We also provide evidence for Gal-9 binding sites on human neutrophils; Gal-9 binding induced neutrophil activation (increased expression of β2 integrins and reduced expression of CD62L). Intra-vital microscopy confirmed a pro-recruitment role for Gal-9, with increased numbers of transmigrated neutrophils following Gal-9 administration. We studied the role of both soluble and immobilized Gal-9 on human neutrophil recruitment. Soluble Gal-9 significantly strengthened the interaction between neutrophils and the endothelium and inhibited neutrophil crawling on ICAM-1. When immobilized, Gal-9 functioned as an adhesion molecule and captured neutrophils from the flow. Neutrophils adherent to Gal-9 exhibited a spread/activated phenotype that was inhibited by CD18 and CD44 neutralizing antibodies, suggesting a role for these molecules in the pro-adhesive effects of Gal-9. Our data indicate that Gal-9 is expressed and released by the activated endothelium and functions both in soluble form and when immobilized as a neutrophil adhesion molecule. This study paves the way for further investigation of the role of Gal-9 in leukocyte recruitment in different inflammatory settings.

Item Type: Article
Uncontrolled Keywords: Neutrophils, Animals, Humans, Mice, Galectins, Cell Adhesion, Transendothelial and Transepithelial Migration, Human Umbilical Vein Endothelial Cells, CD18 Antigens, Hyaluronan Receptors
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User: Symplectic Admin
Date Deposited: 17 May 2022 13:44
Last Modified: 10 Jul 2022 11:39
DOI: 10.1096/fj.202100832r
Open Access URL: https://faseb.onlinelibrary.wiley.com/doi/10.1096/...
URI: https://livrepository.liverpool.ac.uk/id/eprint/3154994