Metabolic and morphologic effects of colchicine on human T-lymphocyte expression of Fcμ, and Fcγ receptors

Abstract

The influence of colchicine on human T-cell fcμ- and Fcγ-receptor expression during culture was studied utilizing a rosette technique with bovine erythrocytes coated with IgM (EOx-IgM) or IgG (EOx-IgG). Treatment of T cells with ⩾10 −6 M concentrations of colchicine induced in these cells progressive loss of microtubules and surface microvilli, inhibited their fcμ−, but not Fcγ-receptor expression during culture, and increased their cyclic AMP levels. However, similar treatment of cells with lumicolchicine, a photoinactivated isomer, identically inhibited the T-cell Fcμ-receptor expression as well, without inducing loss of microtubules or microvilli or raising cyclic AMP levels in them. A direct influence on T-cell protein synthesis by either colchicine or lumicolchicine is likely, as ⩾10 −6 M concentrations of alkaloid identically inhibited [3H]leucine incorporation and Fcμ-receptor expression by T cells without inhibiting their α-methyl isobutyric acid transport. No impairment of optimal EOx-IgM rosette formation occurred in control T lymphocytes cultured for 24 hr and then treated with colchicine, which suggests that its effects did not directly influence the receptor-ligand interaction itself. These findings suggest colchicine has several sites of action on T cells, dependent and independent of microtubular depolymerization, which may be responsible for alterations of T-lymphocyte cellular metabolism and function.