NITRIC OXIDE-RELEASING PARTICLES INHIBIT PHAGOCYTOSIS IN HUMAN NEUTROPHILS

We have constructed a yeast (Saccharomyces cerevisiae) particle capabl e of releasing NO, by loading heat-killed yeast particles with a hydro phobic NO-generating substance, GEA-5171. This particle decreased phag ocytosis in solution, as measured with flow cytometry, to about 80% of control values, Phagocytosis on a surface, as counted under the micro scope, was also decreased by about 20%, The nitric oxide furthermore c ounteracted the production of oxygen metabolites by neutrophils to abo ut 20% of control values, The inhibitory effect was most pronounced fo r the intracellular production, as could be seen when neutrophils prei ncubated with NO-releasing particles were stimulated with chemotactic agent (FMLP) or phorbol ester (PMA), In conclusion, NO has inhibitory effects on both phagocytosis and the respiratory burst of neutrophils. Since nitric oxide is a hydrophobic gas and an air pollutant, there i s a possibility that it accumulates in particles which then become mor e resistant to elimination. (C) 1997 Academic Press.