Summary
Retinoids are known to modulate several functions of mononuclear phagocytes. We have
studied the effect of retinyl acetate (RAc) and retinoic acid (RA) on the production
of procoagulant activity (PCA) by human peripheral blood mononuclear cells stimulated
with endotoxin (1 εg/ml, 4 or 20 h at 37°C). Both compounds caused a dose-dependent
reduction in the expression of cell-associated PCA (from 86 to <10% of control in
the range of concentration comprised between 0.1 and 100 εM). This effect was also
observed when the cells were exposed to retinoids for 10 min and washed before challenge
with endotoxin, indicating that it is rapid and irreversible. In contrast, incubation
of RAc or RA for 3 h at 37° C with cells that have been already stimulated with endotoxin
(20 h at 37° C) remained without influence on cell PCA. The inhibitory action of retinoids
was also observed when monocyte-enriched (>85%) preparations or highly purified monocyte-derived
macrophages (>99%) were used instead of whole mononuclear cells. BW755C, an inhibitor
of cyclo-oxygenase and lipoxygenase, reversed the inhibitory effect of retinoids,
whereas acetylsalycilic acid, an inhibitor of cyclo-oxygenase, was inactive, suggesting
the involvement of a lipoxygenase product. The inhibition of monocyte/macrophage PCA
production and the subsequent reduction of cell potential for fibrin deposition might
represent one of the mechanisms whereby retinoids exert their antiinflammatory and
immunomodulatory activities.
