A comparative study of the effects of quercetin and its glucuronide and sulfate metabolites on human neutrophil function in vitro

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 β2-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.