Inhibition of CD3-induced Ca2+ signals in Jurkat T-cells by myristic acid.
Stimulation of T lymphocytes with antibodies against the T cell receptor/CD3 complex induces within seconds a rise in the concentration of intracellular free Ca2+. Here we show that treatment with 20 microM free myristic acid completely inhibits this Ca2+ signal and the cellular proliferation in Jurkat T cells. Also lauric acid inhibited cell growth while its blocking effect on the Ca2+ signal was weaker than that of myristic acid. Other saturated free fatty acids were inactive. The inhibitory effect of myristic acid could be reversed by the addition of fatty acid free albumin, which will bind the fatty acid. Myristic acid, but not its methyl ester, inhibited both the anti-CD3-induced Ca2+ influx across the cell membrane and Ca2+ release from intracellular stores, but not the formation of inositol phosphates. In contrast, thapsigargin-induced release of Ca2+ from the same intracellular stores was unaffected by myristic acid. Thus, myristic acid specifically blocks T cell antigen receptor-CD3 induced Ca2+ mobilization in T cells.
Nordström
T
T
Department of Pathology, University of Helsinki, Finland.
Lindqvist
C
C
Ståhls
A
A
Mustelin
T
T
Andersson
L C
LC
D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000502:physiology*; D017252:CD3 Complex; D002118:Calcium / Q000378:metabolism*; D002455:Cell Division; D006801:Humans; D007850:Lauric Acids / Q000494:pharmacology; D016853:Muromonab-CD3 / Q000276:immunology; D019814:Myristic Acid; D009227:Myristic Acids / Q000494:pharmacology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D014407:Tumor Cells, Cultured
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007850:Lauric Acids; D016853:Muromonab-CD3; D009227:Myristic Acids; D011948:Receptors, Antigen, T-Cell; D013729:Terpenes; D019814:Myristic Acid; C030358:lauric acid; D019284:Thapsigargin; D002118:Calcium