Effects of short chain fatty acids on effector mechanisms of neutrophils

Abstract

Short chain fatty acids (SCFAs) are metabolic by products of anerobic bacteria fermentation. These fatty acids, despite being an importat fuel for colonocytes, are also modulators of leukocyte function. The aim of this study was to evaluate the effects of SCFAs (acetate, propionate, and butyrate) on function of neutrophils, and the possible mechanisms involved. Neutrophils obtained from rats by intraperitoneal lavage 4 h after injection of oyster glycogen solution (1%) were treated with non toxic concentrations of the fatty acids. After that, the following measurements were performed: phagocytosis and destruction of Candida albicans, production of ROS (O2•-, H2O2, and HOCl) and degranulation. Gene expression (p47phox and p22phox) and protein phosphorylation (p47phox) were analyzed by real time reverse transcriptase chain reaction (RT-PCR) and Western blotting, respectively. Butyrate inhibited phagocytosis and killing of C. albicans. This SCFA also had an inhibitory effect on production of O2•-, H2O2, and HOCl by neutrophils stimulated with PMA or fMLP. This effect of butyrate was not caused by modulation of expression of NADPH oxidase subunits (p47phox and p22phox) but it was in part due to reduced levels of p47phox phosphorylation and an increase in the concentration of cyclic AMP. Acetate increased the production of O2•- and H2O2 in the absence of stimuli but had no effect on phagocytosis and killing of C. albicans. Propionate had no effect on the parameters studied. These results suggest that butyrate can modulate neutrophil function and thus could be important in inflammatory neutrophil-associated diseases. Copyright © 2008 John Wiley & Sons, Ltd.