Generation of 8-Epiprostaglandin F by Human Monocytes
Population
Human monocytes
Design
Preclinical
Authors
Discussion
Loading...
Member takes
Implication
May implicate monocyte-derived isoprostanes in vascular pathology; hypothesis-generating for PG G/H S-2 inhibition in cardiovascular disease.
Key Points
- To determine the biosynthetic pathways responsible for the formation of the vasoconstrictor 8-epi-PGF2alpha in human monocytes, focusing on enzymatic synthesis by PG G/H S-2 versus free radical catalysis.
- Inhibited constitutive PG G/H S-1 in human monocytes using aspirin, then induced PG G/H S-2 expression with concanavalin A, phorbol 12-myristate 13-acetate, or bacterial lipopolysaccharide.
- Assessed enzymatic dependency by treating cells with dexamethasone, cycloheximide, or the selective PG G/H S-2 inhibitor L 745,337.
- Evaluated free radical-mediated formation by exposing monocytes to low density lipoprotein and opsonized zymosan in the presence or absence of antioxidants and superoxide dismutase.
- Induction of PG G/H S-2 stimulated the production of 8-epi-PGF2alpha, PGE2, and TxB2, which was completely blocked by dexamethasone, cycloheximide, and the specific PG G/H S-2 inhibitor L 745,337.
- Coincubation of low density lipoprotein with zymosan-activated monocytes caused substantial 8-epi-PGF2alpha, lipid hydroperoxide, and thiobarbituric acid-reactive substance generation without inducing PG G/H S-2 or forming PGE2 and TxB2.
- Free radical-mediated 8-epi-PGF2alpha and lipid peroxidation generation was markedly suppressed by butylated hydroxytoluene and superoxide dismutase, but was unaffected by L 745,337.
Structured PICO
P
Population
Human monocytes
I
Intervention
Stimulation with concanavalin A, phorbol 12-myristate 13-acetate, bacterial lipopolysaccharide, or opsonized zymosan with low density lipoprotein, and inhibition with dexamethasone, cycloheximide, L 745,337, butylated hydroxytoluene, or superoxide dismutase
O
Outcome
Formation of 8-epi-PGF2alphasurrogate
Human monocytes can generate the mitogen and vasoconstrictor 8-epi-PGF2alpha through both free radical and PG G/H S-2 enzyme-catalyzed pathways, suggesting inducible PG G/H S-2 is an in vivo source of this compound.
Cite This Study
Praticò et al. (1996) studied this question.