Mast cells as a source of superoxide anions and nitric oxide-like factor: relevance to histamine release.
Rat serosal mast cells (MCs, 85-90% pure), obtained from peritoneal washing of Wistar albino rats, produced a significant amount of superoxide anions (O2.-) as measured by the increase in absorbance due to the reduction of ferricytochrome c; they were also able to generate a nitric oxide (NO)-like factor, as measured by two bioassay systems: i) inhibition of platelet aggregation and ii) stimulation of MCs guanylate cyclase. Incubation of MCs with human washed platelets resulted in an inhibition of thrombin-induced platelet aggregation which was proportional to cell number. The inhibitory activity of MCs was potentiated by substances which preserve NO (superoxide dismutase, SOD), and reversed by compounds which inactivate NO (oxyhaemoglobin, oxyHb) or which inhibit its synthesis (NG-monomethyl-L-arginine, MeArg). Mechanical stimulation of MCs produced a time-dependent increase in the levels of their cGMP but not cAMP; this increase was enhanced by E. coli lipopolysaccharide (LPS). NO generators such as sodium nitroprusside (NaNp) also augmented the levels of cGMP in MCs. NaNp inhibited in a dose-dependent manner the release of histamine evoked by compound 48/80 (0.5 microgram/ml), but not by the O2.--generating system (xanthine-xanthine oxidase), suggesting a bidirectional regulation of histamine release afforded by O2.- and NO.
Mannaioni
P F
PF
Department of Preclinical and Clinical Pharmacology, University of Florence, Italy.
Masini
E
E
Pistelli
A
A
Salvemini
D
D
Vane
J R
JR
D000818:Animals; D002452:Cell Count; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D003574:Cytochrome c Group; D004305:Dose-Response Relationship, Drug; D006636:Histamine Release; D006801:Humans; D008070:Lipopolysaccharides / Q000502:physiology; D008297:Male; D008407:Mast Cells / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology; D009569:Nitric Oxide / Q000032:analysis* / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013481:Superoxides / Q000032:analysis* / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology; D013997:Time Factors; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D003574:Cytochrome c Group; D008070:Lipopolysaccharides; D013481:Superoxides; D009599:Nitroprusside; D009569:Nitric Oxide; D003189:p-Methoxy-N-methylphenethylamine; D013917:Thrombin; D006152:Cyclic GMP