Inhibition by nitric oxide-donors of human polymorphonuclear leucocyte functions

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Abstract
1 The study was designed to test the hypothesis that nitric oxide (NO)-releasing compounds increase guanosine 3′:5′-cyclic monophosphate (cyclic GMP) production in human polymorphonuclear leucocytes (PMNs) and concomitantly inhibit PMN functions, i.e. leukotriene B4 (LTB4) synthesis, 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-penicillamine (SNAP). 2 GEA 3162 and GEA 5024 (1–100 μm) inhibited Ca ionophore A23187-induced LTB4 and β-glucuronidase release, chemotactic peptide FMLP-induced chemotaxis and opsonized zymosan-triggered chemiluminescence dose-dependently in human PMNs. SIN-1 and SNAP were weaker inhibitors. 3 Cellular cyclic GMP production was increased after exposure to NO-donors concomitantly with the inhibition of PMN functions. No alterations in the levels of adenosine 3′:5′-cylic monophosphate (cyclic AMP) were detected. 4 The results suggest that NO, possibly through increased cyclic GMP, inhibits the activation of human PMNs and may thus act as a local modulator in inflammatory processes.

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