Metabolic and morphologic effects of colchicine on human T-lymphocyte expression of Fc mu and Fc gamma receptors.
The influence of colchicine on human T-cell Fc mu- and Fc gamma-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 greater than or equal to 10(-6) M concentrations of colchicine induced in these cells progressive loss of microtubules and surface microvilli, inhibited their Fc mu-, but not Fc gamma-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 Fc mu-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 greater than or equal to 10(-6) M concentrations of alkaloid identically inhibited [3H]leucine incorporation and Fc mu-receptor expression by T cells without inhibiting their alpha-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.
D003078:Colchicine / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D007075:Immunoglobulin M; D008162:Lumicolchicines / Q000494:pharmacology; D008870:Microtubules / Q000502:physiology; D014176:Protein Biosynthesis; D011961:Receptors, Fc / Q000378:metabolism*; D017452:Receptors, IgG; D012397:Rosette Formation; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D014529:Uridine / Q000378:metabolism
D007075:Immunoglobulin M; D008162:Lumicolchicines; D011961:Receptors, Fc; D017452:Receptors, IgG; C035311:immunoglobulin M receptor; D000242:Cyclic AMP; D003078:Colchicine; D014529:Uridine