COLCHICINE INTERFERES WITH L-SELECTIN AND LEUKOCYTE FUNCTION-ASSOCIATED ANTIGEN-1 EXPRESSION ON HUMAN T-LYMPHOCYTES AND INHIBITS T-CELL ACTIVATION

Colchicine, which inhibits cell microtubule assembly by preventing pol ymerization of tubulin monomers, inhibits cell-mediated immune respons es and promotes long-term survival of major histocompatibility complex -incompatible renal allografts in rats. Here we evaluated the effect o f blocking cell microtubule assembly by colchicine on T cell and endot helial cell adhesion receptors involved in transducing signals for T c ell activation, By using immunofluorescence flow cytometry analysis, e vidence is presented that colchicine, in a dose-dependent fashion, dow nregulated L-selectin and leukocyte function-associated antigen-1, but not CD2 and CD44 on the surface of naive human peripheral blood lymph ocytes, This effect was confirmed in two subsets of T lymphocytes, nam ely, CD45RA- and CD45RO-positive cells. However, colchicine did not in fluence the rapid shedding of L-selectin from T lymphocytes exposed to activating stimuli. Colchicine inhibited expression of interleukin-2 receptor on activated T lymphocytes. This effect was observed when T l ymphocytes were stimulated with both anti-CDS and anti L-selectin mono clonal antibodies. Colchicine also inhibited lymphocyte function in vi tro as documented by inhibition of the human mixed lymphocyte response in a dose-dependent fashion. Moreover, colchicine downregulated surfa ce expression of intercellular adhesion molecule-1 and E-selectin on a ctivated human umbilical vein endothelial cells. These results indicat e that blocking cell microtubule assembly inhibits surface expression of adhesion molecules on T cells and endothelial cells, and provides i nsights into the complex mechanisms of the action of colchicine in viv o.