Inhibition by glucocorticoids of endocytosis in a macrophage-like cell line

A macrophage-like cell line (P388D1) has been used to demonstrate that glucocorticoids inhibit the fluid-phase endocytosis of fluorescein-labeled dextran (FITC-dextran). Initial experiments demonstrated that the interaction of FITC-dextran with cells had all the features of fluid-phase uptake, ie, the amount taken up was proportional to the concentration in the medium, the uptake proceeded continuously with time and was blocked at 4 degrees C. Dexamethasone (10(-7) M) had no effect on endocytosis until 11 hours after addition of the steroid, when it inhibited the uptake of FITC-dextran by 35%. The amount of inhibition increased with longer exposure times to the hormone up to 50% after 22 hours. Although this effect on endocytosis was observed prior to any effect on growth of the cells, endocytosis as well as cell proliferation were inhibited in a dose dependent fashion. A preliminary survey of selected steroids has established that the inhibition of endocytosis was restricted to steroids of the glucocorticoid class. The key experiments were also performed using horseradish peroxidase instead of FITC-dextran with, essentially, identical results.