Regulation of phospholipid metabolism by K+ channel blockers and inhibitors of choline transport in the Jurkat T cell line. Relationships with cell proliferation and interleukin-2 production.
In the human T cell line Jurkat, three drugs generally used as effectors of K+ channels, i.e., quinine, 4-aminopyridine and tetraethylammonium, modify phospholipid metabolism. The drugs inhibited the synthesis of both phosphatidylcholine and phosphatidylethanolamine. The mechanism of such inhibition involves a decreased uptake of choline and ethanolamine by the cells, since the three K+ channel blockers were found to be able to competitively inhibit the high-affinity choline/ethanolamine transport system at the membrane level. In contrast, choline transport-inhibitors such as hemicholinium-3, decamethonium and dodecyltrimethylammonium do not inhibit interleukin-2 synthesis and proliferation of the Jurkat T cell line. This indicates that the inhibition of either phosphatidylcholine and/or phosphatidylethanolamine synthesis is not directly implicated in these processes. The inhibition of interleukin-2 synthesis appeared to be mediated through the inhibition of diacylglycerol production induced by T cell activators. A major role for phosphatidylserine in the regulation of T cell activation emerged, since we demonstrated that a panel of K+ channel blockers enhanced the synthesis of this phospholipid mimicking the previously described effect of exogenously added phosphatidylserine in Jurkat cells, i.e., a blockade of interleukin-2 synthesis probably due to a defect in diacylglycerol production.
Aussel
C
C
Interactions Cellulaires en Immunologie, INSERM U343, Faculté de Médecine, Nice, France.
Cattan
N
N
Pelassy
C
C
Rossi
B
B
D015761:4-Aminopyridine / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002794:Choline / Q000378:metabolism / Q000493:pharmacokinetics*; D004075:Diglycerides / Q000096:biosynthesis; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008563:Membrane Lipids / Q000096:biosynthesis; D010718:Phosphatidylserines / Q000096:biosynthesis; D010743:Phospholipids / Q000096:biosynthesis / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects*; D011803:Quinine / Q000494:pharmacology; D017452:Receptors, IgG / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014316:Tritium
D000911:Antibodies, Monoclonal; D004075:Diglycerides; D007376:Interleukin-2; D008563:Membrane Lipids; D010718:Phosphatidylserines; D010743:Phospholipids; D015221:Potassium Channels; D017452:Receptors, IgG; D013757:Tetraethylammonium Compounds; D014316:Tritium; D019789:Tetraethylammonium; D011803:Quinine; D015761:4-Aminopyridine; D002794:Choline