The inhibition by fatty acids of receptor-mediated calcium movements in Jurkat T-cells is due to increased calcium extrusion.
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.
Breittmayer
J P
JP
Interactions Cellularies en Immunologie et Immunopathologie, Institut National de la Santé et de la Recherche Médicale U343, Nice, France.
Pelassy
C
C
Cousin
J L
JL
Bernard
A
A
Aussel
C
C
D000911:Antibodies, Monoclonal / Q000502:physiology*; D017252:CD3 Complex / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002460:Cell Line; D005227:Fatty Acids / Q000494:pharmacology*; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation; D010718:Phosphatidylserines / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D005227:Fatty Acids; D010718:Phosphatidylserines; D013729:Terpenes; D015759:Ionomycin; D019284:Thapsigargin; D000252:Calcium-Transporting ATPases; D002118:Calcium