Oxidative and adhesive responses of human neutrophils to nitrovasodilators in vitro: the role of protein kinases.
BACKGROUND
Sodium nitroprusside (SNP) and molsidomine are used in the treatment of coronary heart disease. Since the neutrophils play a pathological role in ischaemic heart disease, it is important to understand the direct action of nitrovasodilators on their function.


OBJECTIVE
We examined the effects of SNP and 3-morpholinosydnonimine (SIN-1, molsidomine metabolite) on the respiratory burst of human neutrophils and their adhesion in vitro . The influence of nitric oxide (NO)donors on the activity of protein kinases, which are involved in the NADPH oxidase activation, was also investigated.


METHODS
The respiratory burst of neutrophils was determined by chemiluminescence and fluorescence methods, while the adhesion was assayed by adherence of neutrophils to the plastic surface.


RESULTS
NO donors decreased the oxidative burst of activated neutrophils. However, the effects of SNP and SIN-1 strongly depended on the treatment time of neutrophils and on the stimulus employed to cells activation. Protein kinase C inhibitor did not prevent the inhibitory effect of SIN-1, but diminished the inhibitory effect of SNP on the neutrophils' respiratory burst. Protein tyrosine kinase inhibitor did not affect the action of SNP, but diminished the inhibitory effect of SIN-1 on fMLP-stimulated but not on PMA stimulated oxidative burst of neutrophils. This suggests that SNP action is mainly associated with protein kinase C, while SIN-1 is associated with protein tyrosine kinase activity. We also found that SIN-1 but not SNP diminished the adhesive activity of neutrophils.


CONCLUSIONS
Our data show that SIN-1 biological effect on some neutrophils activity is different from both spermine NONOate and SNP, and mainly depends on ONOO(-), while SNP action is mediated by NO.
Klink
Magdalena
M
Microbiology and Virology Centre, Polish Academy of Sciences, Lodowa 106, 93-232 Lodz, Poland. MKlink@poczta.onet.pl
Tchorzewski
Henryk
H
Sulowska
Zofia
Z
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D010084:Oxidation-Reduction; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D011494:Protein Kinases / Q000187:drug effects / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000187:drug effects / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D009599:Nitroprusside; D009240:N-Formylmethionine Leucyl-Phenylalanine; C002385:linsidomine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D008981:Molsidomine; D019833:Genistein; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate