Prostasomes inhibit the NADPH oxidase activity of human neutrophils

Prostasomes are particular lipid vesicles secreted by the prostate in human semen and involved in several physiological functions such as the improvem ent of sperm motility or immunomodulation. We have previously shown that th ey reduced the overall reactive oxygen species (ROS) production of seminal polymorphonuclear neutrophils (PMN). The present study was conducted to def ine the mechanism by which prostasomes inhibit the ROS production of blood and seminal PMN. The luminol chemiluminescence measuring total ROS producti on of blood PMN stimulated by either a phorbol ester (PMA) or a chemoattrac tant peptide, formyl-Met-Leu-Phe (fMLP) was significantly inhibited by pros tasomes. The NADPH oxidase activity of the PMN was measured by 2-methyl-6-( p-methoxyphenyl)-3,7-dihydroimidazo[1,2-a]pyrazin-3-one (MCLA) chemilumines cence. Prostasomes inhibited the NADPH oxidase activity of blood or seminal PMN and increased the lag-phase of the enzyme after PMA stimulation. Prost asomes also inhibited significantly the NADPH oxidase activity of fMLP stim ulated blood PMN, but the inhibition was not significant for seminal PMN. T he lipid composition of blood PMN was analysed and compared to the lipid co mposition of prostasomes. This showed that prostasomes had a high cholester ol:phospholipid molar ratio and a high proportion of sphingomyelin. Togethe r with the fact that prostasomes can rigidify the plasma membrane of blood PMN, these results led us to postulate that prostasomes inhibit the NADPH o xidase activity of PMN by lipid transfer from the prostasomes to the plasma membrane of the PMN.