Nitric Oxide-releasing Particles Inhibit Phagocytosis in Human Neutrophils

We have constructed a yeast (Saccharomyces cerevisiae) particle capable of releasing NO, by loading heat-killed yeast particles with a hydrophobic NO-generating substance, GEA-5171. This particle decreased phagocytosis in solution, as measured with flow cytometry, to about 80% of control values. Phagocytosis on a surface, as counted under the microscope, was also decreased by about 20%. The nitric oxide furthermore counteracted the production of oxygen metabolites by neutrophils to about 20% of control values. The inhibitory effect was most pronounced for the intracellular production, as could be seen when neutrophils preincubated 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 is a possibility that it accumulates in particles which then become more resistant to elimination.