Abstract
Numerous studies on the molecular basis of the mechanism of action of fatty acids have demonstrated their action in cell signaling and particularly on the regulation of cytosolic Ca2+ concentration. Stimulation of Jurkat T cells with CD3 monoclonal antibody results in an increase of intracellular calcium concentration, [Ca2+]i due both to a release of Ca2+ from intracellular stores and a Ca2+ influx. [Ca2+]i increase represents a dynamic balance between Ca2+ influx and efflux. Fatty acids, either saturated (C14:0), monounsaturated (C16:1), or polyunsaturated, belonging to the C18 and the C20 series induce a marked decrease of CD3-induced [Ca2+]i rise. This property of fatty acid is independent of the position of the carbon-carbon double bond but specific of the cis stereoisomeric form. Fatty acids does not block CD3-induced signals but greatly stimulates the Ca2+ extrusion process probably by activating the plasma membrane Ca(2+)-ATPase. This was documented by the observation that fatty acids, reduced to the same extent as [Ca2+]i, elicited either with CD3 monoclonal antibody the calcium ionophore ionomycin or the Ca(2+)-ATPase inhibitor thapsigargin.
Highlights
Numerous studies on the molecbualsairsof the mech- established since myristic acid has been described [7] to block anism of action ofatty acids have demonstrated their both the release of Ca2+from intracellular stores as well as action incell signaling and particularlyon the regula- Ca2+influx induced by CD3
Jurkat T cells with CD3 monoclonal antibody results release of Ca2+from the endoplasmic reticulum [5] and to siad[(nCCtcyoain1adr"a6nese]m:s,i1tidanhi)ucn,ceoesdrrrabebatapaoulsotCarhelanyatocu2tefeo+ndiisannbafrtetlruteuwalrxecae.aete[selnCle(duC,aolCaf12br+a4Ce2:Ilca0oi+a2)nil+,ncginicimfunrrfmlgoeouamnxtscoioeenoufatfnrtnnrlhecusadCepeaxcnrt1e.uetFl8rrlsuaaeaatlnttnatietdyordsna, bbmpCleoaoaei2ccnn+krtossep,htxhhowtearweugnsreheistoaco,nveapaerianctocttaeihrcvs-itmatdievtoeedandtiCie1cad8atae2cfd+iadt-cCtAaeylanTl2sdaP.+cdaiIiodsnnecsfr,oleowussraxuidthilehnterixndtagiToefifnnecocrleiaeaclcnrlaicstfceyic(lde6atrh)hra.baetoveIsnneed the C20 series induce a marked decrease of CD3-in- chain lengths and different unsaturation degrees on CD3, duced [Ca'+l~rise
Clone D was selected omycin or the Ca2+-ATPase inhibitor thapsigargin. on the base of its interleukin-2 production when activated with phytohemagglutinin and the phorbolester, 12-0-tetradecanoylphorbol-13-acetate
Summary
Documentedbythe observationthat fatty acids, re- Cells-The human T cell line Jurkat was kindly supplied by Dr A. The inhibitory effect of fatty acids involves perturbation of transmembrane signaling in cytotoxic T lymphocytes [3] and in T cell lines [4, 5] as well as in macrophages [6]. Unsaturated fatty acids inhibit receptor-mediated calcium in- After an incubation period of 1 h, the cells were rapidly sedimented flux in T cells. This effect appeared to be specific of the unsaturation degree of the fattyacid since saturated ones did not change the Ca2+signaling process. The analyses were performed on a fluorescence-activated article were defrayed in part by the payment of page charges This cell sorter (FACStar plus, Becton Dickinson).
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