Retinoids upregulate phagocytosis by human dermal microvascular endothelial cells.
Animals fed a diet deficient in vitamin A show severe physiological changes that often result in death. At the cellular level, retinoids have been shown to induce differentiation of cells derived from a wide spectrum of tissues, including the vasculature. To understand further the mechanisms for these events, we studied the effects of 13-cis-retinoic acid, all-trans-retinoic acid, all-trans-retinol, and all-trans-retinol acetate on human dermal microvascular endothelial cells (HDMEC). Concentrations of retinoids in the physiological range from 0 to 1 microM were used in our experiments. These concentrations were nontoxic to HDMEC. Here we report that in addition to the known effect of retinoids on keratinocytes and sebacytes, retinoids induced morphological and functional changes in HDMEC that gave these cells macrophage like characteristics. 13-Cis-retinoic acid and all-trans-RA induced HDMEC to phagocytize and to increase the production of hydrogen peroxide and superoxide anion. These two retinoids also changed the morphology of endothelial cells from typical small compact cuboidal epithelioid cells to cells with larger cytoplasm and indistinct cell membranes. The retinoid-stimulated HDMEC deposited increased amounts of extracellular matrix. All-trans-retinol and all-trans-retinol acetate did not significantly affect HDMEC in all parameters tested. The induction of these properties provides a new model with which to study how retinoids regulate gene expression using a normal, nontransformed cell line.
Vora
M
M
Department of Dermatology, Stanford University Medical Center, Stanford University, California 94305-5468.
Karasek
M A
MA
D002478:Cells, Cultured; D003078:Colchicine / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007231:Infant, Newborn; D007700:Kinetics; D008297:Male; D008833:Microcirculation; D010587:Phagocytosis / Q000187:drug effects*; D012176:Retinoids / Q000494:pharmacology*; D012867:Skin / Q000098:blood supply; D013329:Structure-Activity Relationship; D013481:Superoxides / Q000378:metabolism*
D012176:Retinoids; D013481:Superoxides; D003609:Dactinomycin; D003571:Cytochalasin B; D003513:Cycloheximide; D003078:Colchicine