Signal transduction pathways affected by nitric oxide donors during neutrophil functional response in vitro.
OBJECTIVE
We investigated the intracellular signalling pathways by which nitric oxide (NO) donors: diethylamine/NO (DEA/NO) and 3-morpholinosydnonimine (SIN-1) regulate the functional response of human neutrophils to activating stimuli.


METHODS
The phosphorylation and nitration of signalling proteins, cyclic GMP level, neutrophil respiratory burst and adhesive activities and CD11b/CD18 molecule expression on neutrophils in the presence and absence of soluble guanylate cyclase inhibitors were determined.


RESULTS
NO donors showed strong inhibitory effect on activated neutrophils. NO donors nitrated the tyrosine residues in signalling proteins causing a decrease in tyrosine phosphorylation and neutrophils response to activation. Diethylamine/NO employed cyclic GMP as a signalling molecule in its action on neutrophils, whereas peroxynitrite anion donor affected neutrophil functions in a cGMP-independent manner. Moreover, we observed that peroxynitrite anion can overcome the nitric oxide molecule action.


CONCLUSIONS
We conclude that each NO donor depending on its concentration and chemical nature may act on different elements of neutrophil signalling pathways capable of inducing distinct neutrophil functions.
Klink
M
M
Centre for Medical Biology, Polish Academy of Sciences, 93-232, Lodz, Lodowa 106, Poland. mklink@cbm.pan.pl
Bednarska
K
K
Jastrzembska
K
K
Banasik
M
M
Sulowska
Z
Z
D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D002448:Cell Adhesion; D006152:Cyclic GMP / Q000378:metabolism; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D006834:Hydrazines / Q000378:metabolism; D008981:Molsidomine / Q000031:analogs & derivatives / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism; D018375:Neutrophil Activation / Q000502:physiology; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000378:metabolism*; D016897:Respiratory Burst; D015398:Signal Transduction / Q000502:physiology*
D039481:CD11b Antigen; D018821:CD18 Antigens; D006834:Hydrazines; C509295:ITGAM protein, human; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D009240:N-Formylmethionine Leucyl-Phenylalanine; C002385:linsidomine; C084012:1,1-diethyl-2-hydroxy-2-nitrosohydrazine; D008981:Molsidomine; D006162:Guanylate Cyclase; D006152:Cyclic GMP