Regulation of interleukin-2 production and phosphatidylserine synthesis in Jurkat T lymphocytes by K+ channel antagonists.
Modification of phospholipid metabolism during T cell activation has been repeatedly reported. Recently, we have shown that phytohaemagglutinin, CD3 and CD2 mAbs, which are potent in vitro activators of helper T lymphocytes, markedly inhibit phosphatidylserine synthesis concomitantly as they induce the secretion of IL-2. In this paper, we show evidence that in T lymphocytes K+ channels, which have been shown to participate in the cell activation process, are also reciprocally related to phosphatidylserine synthesis. In fact, in resting T cells the drugs affecting the activity of K+ channels, such as quinine and 4-aminopyridine, induce a rise of phosphatidylserine synthesis. In activated cells, quinine and 4-amidopyridine also caused a rise in phosphatidylserine synthesis which paralleled a decreased production of IL-2, strongly suggesting that these two events are correlated in a reciprocal manner. More precisely, phosphatidylserine synthesis was stimulated by drugs which have been reported to inhibit potassium channels in lymphocytes, e.g. quinine, 4-aminopyridine, tetraethylammonium. These data suggest that the decreased PS synthesis observed during T cell activation intervenes in the cascade of events leading to IL-2 secretion. The decrease in the biosynthesis of this phospholipid seems to be dependent on the activity of K+ channels.
Aussel
C
C
Unité de Recherches en Immunologie Cellulaire et Moléculaire, INSERM U210 Faculté de Médecine (Pasteur), Nice, France.
Pelassy
C
C
Mary
D
D
Choquet
D
D
Rossi
B
B
D015761:4-Aminopyridine / Q000494:pharmacology; D002460:Cell Line; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis*; D010718:Phosphatidylserines / Q000096:biosynthesis*; D010835:Phytohemagglutinins / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011803:Quinine / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
D007376:Interleukin-2; D010718:Phosphatidylserines; D010835:Phytohemagglutinins; D015221:Potassium Channels; D011803:Quinine; D015761:4-Aminopyridine