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

Norberto Perico, Daniel Ostermann, Mario Bontempelli, Marina Morigi, C. Susana Amuchastegui, Carla Zoja, Enver Akalin, Mohamed H. Sayegh, Giuseppe Remuzzi

Research output: Contribution to journalArticle

32 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)594-601
Number of pages8
JournalJournal of the American Society of Nephrology
Volume7
Issue number4
StatePublished - Apr 1996

Keywords

  • Adhesion molecules
  • Colchicine
  • Endothelial cell
  • T cell
  • T cell receptor

ASJC Scopus subject areas

  • Nephrology

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    Perico, N., Ostermann, D., Bontempelli, M., Morigi, M., Amuchastegui, C. S., Zoja, C., Akalin, E., Sayegh, M. H., & Remuzzi, G. (1996). Colchicine Interferes with L-Selectin and Leukocyte Function-Associated Antigen-1 Expression on Human T Lymphocytes and Inhibits T Cell Activation. Journal of the American Society of Nephrology, 7(4), 594-601.