Inhibition by nitric oxide-donors of human polymorphonuclear leucocyte functions.
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 microM) inhibited Ca ionophore A23187-induced LTB4 and beta-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'-cyclic 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.
Department of Biomedical Sciences, University of Tampere, Finland.
E
E
Moilanen
P
P
Vuorinen
H
H
Kankaanranta
T
T
Metsä-Ketelä
H
H
Vapaatalo
D015550:Cell Degranulation / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D000242:Cyclic AMP / Q000096:biosynthesis; D006152:Cyclic GMP / Q000096:biosynthesis; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000096:biosynthesis; D008163:Luminescent Measurements; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine; D013481:Superoxides / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology
D014230:Triazoles; D013481:Superoxides; C082873:GEA 5024; D007975:Leukotriene B4; D009569:Nitric Oxide; C002385:linsidomine; D026423:S-Nitroso-N-Acetylpenicillamine; C082874:GEA 3162; D008981:Molsidomine; D000242:Cyclic AMP; D005966:Glucuronidase; D010396:Penicillamine; D006152:Cyclic GMP