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 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 microfubule 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.
Perico
N
N
Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Ostermann
D
D
Bontempeill
M
M
Morigi
M
M
Amuchastegui
C S
CS
Zoja
C
C
Akalin
E
E
Sayegh
M H
MH
Remuzzi
G
G
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015704:CD4 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D003078:Colchicine / Q000494:pharmacology*; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D019041:L-Selectin / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D010703:Phorbol Esters / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D014471:Umbilical Veins
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D019040:E-Selectin; D016169:Lymphocyte Function-Associated Antigen-1; D010703:Phorbol Esters; D015375:Receptors, Interleukin-2; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin; D003078:Colchicine