Human neutrophils transform prostaglandins by a myeloperoxidase-dependent mechanism.

J M Paredes,S J Weiss

doi:10.1016/s0021-9258(19)81021-9

Abstract

Intact human neutrophils, incubated with the soluble stimulant phorbol myristate acetate, discharge lysosomal components, generate oxygen metabolites, and transform exogenous 6-keto-prostaglandin F1 alpha, prostaglandin E2, and prostaglandin F2 alpha as assessed by thin layer radiochromatography. Neutrophils alone were incapable of transforming the prostaglandins. The addition of catalase or the myeloperoxidase inhibitor, azide, protected all three prostaglandins from the phorbol-stimulated neutrophils. Neither superoxide dismutase, heat-inactivated catalase, nor albumin had any inhibitory effect in this system. A model system consisting of glucose-glucose oxidase, as a source of H2O2, purified myeloperoxidase, and chloride was also able to transform the prostaglandins in an identical fashion. Neither glucose-glucose oxidase alone nor glucose-glucose oxidase and myeloperoxidase under chloride-free conditions were able to mediate this transformation. Thus, it appears that intact human neutrophils can transform prostaglandins by a mechanism dependent on H2O2, the lysosomal enzyme myeloperoxidase, and chloride. Given the importance of prostaglandins in regulating immune function, neutrophil-dependent prostaglandin transformation could play a novel role in modulating the inflammatory response.

Highlights

We examined a potential interactionbetween stimulated neutrophilsand the prostaglandins 6-keto-PGF1, PGE2, and PGFZ,.' We have demonstrated that intact human neutrophils can transform these prostaglandins by a mecha
Neutrophil-mediated Transformationof ProstaglandinsHuman neutrophils incubatedwith PMA discharge lysosomal components, generate oxygen metabolites, andmediatea striking transformation of exogenous 6-keto-PGFI, PGEZ, or PGFza asassessed by thin layer radiochromatography (Fig. 1, A, B, and C)
Incubation of the prostaglandins with stimulated neutrophils did not alter the recovery of the labeled compounds and there was no increase in the radioactivity remaining in the aqueous phase after extraction

Summary

Introduction

Neutrophils were stimulated to release lysosomal components sisting of glucose-glucose oxidase,as a source ofHzOz, and generate oxygen metabolites with 20 ng/ml of PMA [8].In the purified myeloperoxidase, and chloride was able cell-free studies, the experiments were performed in an identical to transform the prostaglandinisn an identical fashion. We examined a potential interactionbetween stimulated neutrophilsand the prostaglandins 6-keto-PGF1,, PGE2, and PGFZ,.' We have demonstrated that intact human neutrophils can transform these prostaglandins by a mecha-

Results

Conclusion