THE EFFECT OF SIX PROSTAGLANDINS, PROSTACYCLIN AND ILOPROST ON GENERATION OF SUPEROXIDE ANIONS (0J) BY HUMAN NEUTROPHILS (PMNs) ACTIVATED BY ZYMOSAN OR FMLP

Human PMNs in a suspension (2.5 - 3.5 × 10⁶ cells/ml of PBS) were activated by opsonized zymosan (2.5 mg/ml) or by FMLP (22 jjg/ml) in presence or absence of prostaglandins (PG) E₁ E₂, D₂, 6-keto-F_2α, 6-keto-E₁ prostacyclin and Iloprost (3nM -30 pM). The generation of superoxide anions was measured as a SOD-sensitive reduction of ferrocytochrome c. In FMLP-stimulated PMNs an average production of 0^- ₂ of 18 ± 3.2 nmoles/10^- ₂ PMNs/10 min was suppressed by 25% at following concentrations of PGD2, PGE2, PGE1s 6-keto-PGE! and PGF2 : 0.1, 0.2, 0.5, 0.8 and>30.0 pM, respectively. No significant inhibition occurred in the presence of prostacyclin, 6-keto-PGF₂ and Iloprost at concentrations as high as 30 pM. In zymosan-stimulated PMNs prostaglandins of E series were less potent inhibitors than in FMLP-stimulated PMNs by following factors: PGE₂ - 20, 6-keto-PGE₂ - 13, PGE₁ - 4, whereas PGD2 was equally potent inhibitor in FMLP- and zymosan-stimulated PMNs. It is concluded that PGE₂ is an antagonist of FMLP-receptor-mediated events which are responsible for the generation of superoxide anions in PMNs, whereas its isomer PGD₂ has another mechanism of the 0^- ₂-suppressive action. Perhaps, PGD₂ is a direct inhibitor of membrane-bound NADPH-oxidase or an antagonist of oxygen activation by leukotrienes and lipoxins or a promotor of scavenging of 0^- ₂ by mitochondrial membranes. The latter mechanism has been proposed recently by Gryglewski as explanation for cytoprotective action of stable biologically active metabolites of prostacyclin. Mechanisms of anti-0^- ₂ action of PGE₁ and 6-keto-PGE₁ in PMNs are likely to be intermediate between these proposed for PGE₂ and PGD₂.