INHIBITION BY NITRIC-OXIDE DONORS OF HUMAN POLYMORPHONUCLEAR LEUKOCYTE FUNCTIONS

1 The study was designed to test the hypothesis that nitric oxide (NO) -releasing compounds increase guanosine 3':5'-cyclic monophosphate (cy clic GMP) production in human polymorphonucicar leucocytes (PMNs) and concomitantly inhibit PMN functions, i.e. leukotriene B4 (LTB4) Synthe SiS, degranulation, chemotaxis and superoxide anion (O2-) release. The effects of two new NO-releasing compounds, GEA 3162 and GEA 5024 were compared to 3-morpholino-sydnonimine (SIN-1) and S-nitroso-N-acetyl-p enicillamine (SNAP). 2 GEA 3162 and GEA 5024 (1-100 mum) inhibited Ca ionophore A23187-induced LTB4 and beta-glucuronidase release, chemotac tic peptide FMLP-induced chemotaxis and opsonized zymosan-triggered ch emiluminescence dose-dependently in human PMNs. SIN-1 and SNAP were we aker inhibitors. 3 Cellular cyclic GMP production was increased after exposure to NO-donors concomitantly with the inhibition of PMN functio ns. No alterations in the levels of adenosine 3':5'-cyclic monophospha te (cyclic AMP) were detected. 4 The results suggest that NO, possibly through increased cyclic GMP, inhibits the activation of human PMNs a nd may thus act as a local modulator in inflammatory processes.