RT Journal Article
T1 Regulation of neutrophil function by selective targeting of glycan epitopes expressed on the integrin CD11b/CD18
A1 Azcutia Criado, Verónica
A1 Kelm, Matthias
A1 Lehoux, Sylvain
A1 Cummings, Richard D.
A1 Nusrat, Asma
A1 Parkos, Charles A.
A1 Brazil, Jennifer C.
AB Polymorphonuclear neutrophils (PMNs) play a critical role in the innate immune response to invading pathogens. However, dysregulated mucosal trafficking of PMNs and associated epithelial tissue damage is a pathological hallmark of numerous inflammatory conditions including inflammatory bowel disease. The glycoprotein CD11b/CD18 plays a well-described role in regulating PMN transepithelial migration and PMN inflammatory functions. Previous studies have demonstrated that targeting of the N-linked glycan Lewis X on CD11b blocks PMN transepithelial migration (TEpM). Given evidence of glycosylation-dependent regulation of CD11b/CD18 function, we performed MALDI TOF Mass Spectrometry (MS) analyses on CD11b/CD18 purified from human PMNs. Unusual glycan epitopes identified on CD11b/CD18 included high Mannose oligosaccharides recognized by the Galanthus Nivalis lectin and biantennary galactosylated N-glycans recognized by the Phaseolus Vulgaris erythroagglutinin lectin. Importantly, we show that selective targeting of glycans on CD11b with such lectins results in altered intracellular signaling events that inhibit TEpM and differentially affect key PMN inflammatory functions including phagocytosis, superoxide release and apoptosis. Taken together, these data demonstrate that discrete glycan motifs expressed on CD11b/CD18 such as biantennary galactose could represent novel targets for selective manipulation of CD11b function and reduction of PMN-associated tissue damage in chronic inflammatory diseases.
PB Federation of American Societies for Experimental Biology
YR 2019
FD 2019
LK https://hdl.handle.net/20.500.14352/117487
UL https://hdl.handle.net/20.500.14352/117487
LA eng
NO Kelm, Matthias, et al. «Regulation of Neutrophil Function by Selective Targeting of Glycan Epitopes Expressed on the Integrin CD11b/CD18». The FASEB Journal, vol. 34, n.o 2, febrero de 2020, pp. 2326-43. DOI.org (Crossref), https://doi.org/10.1096/fj.201902542R
NO National Institutes of Health (US)
NO Crohn's and Colitis Foundation (US)
DS Docta Complutense
RD 6 abr 2025