Mannose Inhibits the Human Neutrophil Oxidative Burst

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Abstract
Stimulated human neutrophils (PMNs) increase their oxygen consumption and secrete reactive oxygen species that are involved in bactericidal activity and inflammation. While studying lectin-mediated bacterial adherence, we observed that D-mannose appeared to inhibit PMN metabolism. Further studies showed that 100 mM mannose inhibited oxygen consumption by 82%, superoxide secretion by 84%, luminol-enhanced chemiluminescence (CL) by 98%, and hexose-monophosphate shunt activity by 100% when PMN were stimulated with 1 μM phorbol myristate acetate (PMA). Inhibition was also seen with 0.1 μM formyl-methionyl-leucyl-phenylalanine (fMLP), and 0.1 μM A23187, reagents thought to stimulate the respiratory burst by different transductional mechanisms. Inhibition was dose-responsive and specific since 100 mM D-galactose, alpha-D-glucose, or alpha-L-fucose only minimally affected PMN oxidative metabolism. Inhibition of PMA-induced superoxide production was seen almost immediately upon the addition of 50 mM mannose and was reversed by washing. Neutrophils remained viable as measured by trypan blue exclusion. These data suggest that mannose inhibits the neutrophil oxidative burst at the level of the hexose monophosphate shunt. Further investigation should elucidate the specific mechanism(s) of this burst inhibition as well as define uses for it as a tool to study oxidative as well as nonoxidative killing by PMN.