title: A comparative study of the effects of quercetin and its glucuronide and sulfate metabolites on human neutrophil function in vitro.
abstract: Exposure of neutrophils to either lipopolysaccharide (LPS) or N-formyl-methionyl-leucyl-phenylalanine (fMLP) is associated with changes in the expression of cell adhesion molecules and elevation of intracellular calcium ions. Although dietary flavonoids are reported to possess anti-inflammatory properties, little is known regarding the effect of their metabolites. We have investigated the effects of quercetin and its major metabolites on LPS and fMLP-stimulated human neutrophils using concentrations comparable to those reported in feeding studies on human volunteers. The metabolite quercetin 3-glucuronide caused a significant reduction in fMLP-evoked calcium influx in human neutrophils (approximately 35%), while neither quercetin 3'-sulfate nor quercetin produced a similar change. Acute exposure of human neutrophils to LPS altered cell shape and surface expression of CD16, but neither of these events were significantly altered by quercetin, quercetin 3-glucuronide nor quercetin 3'-sulfate. In addition, LPS caused a fivefold up-regulation in the expression of beta(2)-integrin (CD11b/Mac 1) and a concomitant 70% down-regulation of L-selectin (CD62L) adhesion molecule expression in human neutrophils. Neither effect was altered by quercetin, quercetin 3-glucuronide or quercetin 3'-sulfate. In conclusion, we found that acute exposure to quercetin and quercetin 3'-sulfate does not affect either expression of cell adhesion molecules or the elevation of intracellular calcium ions in response to LPS and fMLP in human neutrophils. However, quercetin 3-glucuronide reduced fMLP-evoked calcium responses. While this study highlights that metabolites of quercetin may possess different biological properties, dietary ingestion of quercetin is unlikely to exert a major effect on neutrophil function in vivo.
authors.affiliation: Centre for Integrated Systems Biology and Medicine, School of Biomedical Sciences, Medical School, University of Nottingham, Nottingham NG7 2UH, UK. sunita.suri@nottingham.ac.uk
authors.forename: Sunita
authors.initials: S
authors.lastname: Suri
authors.forename: Moira A
authors.initials: MA
authors.lastname: Taylor
authors.forename: Anne
authors.initials: A
authors.lastname: Verity
authors.forename: Sandra
authors.initials: S
authors.lastname: Tribolo
authors.forename: Paul W
authors.initials: PW
authors.lastname: Needs
authors.forename: Paul A
authors.initials: PA
authors.lastname: Kroon
authors.forename: David A
authors.initials: DA
authors.lastname: Hughes
authors.forename: Vincent G
authors.initials: VG
authors.lastname: Wilson
mesh_terms: D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D017136:Ion Transport; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000276:immunology / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D011794:Quercetin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D017452:Receptors, IgG / Q000096:biosynthesis
chemical_list: D008070:Lipopolysaccharides; D017452:Receptors, IgG; C531389:quercetin 3'-sulfate; C443401:quercetin 3-O-glucuronide; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011794:Quercetin; D002118:Calcium