Effects of retinoic acid on the epidermal Langerhans cells and beta-glucuronidase activity in macaque skin.

Retinoic acid (0.5% in acetone) was applied topically to the back skin of five juvenile rhesus monkeys once a day for 7 successive days. Two control animals were given vehicle alone. Skin specimens were taken from each animal at 0, 1, 2, and 4 weeks. The tissues were prepared for both histology (1-micron plastic sections) and split epidermal sheets (after incubation with EDTA solution, 17 mM). The split epidermal sheets were stained with ATPase and anti-Ia antibody, and the number of Langerhans cells was counted. The activity of beta-glucuronidase in the split epidermis was assayed by Fishman's method. After one week of treatment, the epidermis showed marked acanthosis and hyperkeratosis. The Langerhans cells showed severe degeneration, and the number of cells had dropped to approximately one-third of the number in the control skins. Concomitantly, the activity of beta-glucuronidase in the epidermis had also decreased to one-third of the control levels. After withdrawal, the number of Langerhans cells and activity of beta-glucuronidase showed gradual recovery, and by the fourth week they were back to the ranges of pretreatment or control skins, but acanthotic change remained. The results suggest that retinoid applied topically to normal primate skin induces reversible degeneration and desquamation of the Langerhans cells, while the epidermis shows prolonged proliferative change.