Colchicine Interferes with L-Selectin and Leukocyte Function-Associated Antigen-1 Expression on Human T Lymphocytes and Inhibits T Cell Activation

Abstract

Colchicine, which inhibits cell microtubule assembly by preventing polymerization of tubulin monomers, inhibits cell-mediated immune responses and promotes long-term survival of major histocompatibility complex-incompatible renal allografts in rats. Here we evaluated the effect of blocking cell microtubule assembly by colchicine on T cell and endothelial cell adhesion receptors involved in transducing signals for T cell activation. By using immunofluorescence flow cytometry analysis, evidence is presented that colchicine, in a dose-dependent fashion, downregulated L-selectin and leukocyte function-associated antigen-1, but not CD2 and CD44 on the surface of naive human peripheral blood lymphocytes. This effect was confirmed in two subsets of T lymphocytes, namely, CD45RA- and CD45RO-positive cells. However, colchicine did not influence 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 lymphocytes were stimulated with both anti-CD3 and anti L-selectin monoclonal antibodies. Colchicine also inhibited lymphocyte function in vitro as documented by inhibition of the human mixed lymphocyte response in a dose-dependent fashion. Moreover, colchicine downregulated surface expression of intercellular adhesion molecule-1 and E-selectin on activated human umbilical vein endothelial cells. These results indicate that blocking cell microtubule assembly inhibits surface expression of adhesion molecules on T cells and endothelial cells, and provides insights into the complex mechanisms of the action of colchicine in vivo.