Regulation by sphingomyelinase and sphingosine of Ca2+ signals elicited by CD3 monoclonal antibody, thapsigargin, or ionomycin in the Jurkat T cell line.
Sphingomyelinase induces a marked rapid decrease of cytosolic Ca2+ concentration in Jurkat T cells treated with either CD3 monoclonal antibody; the Ca(2+)-ATPase inhibitor, thapsigargin; or the Ca2+ ionophore, ionomycin. Sphingomyelinase treatment of Jurkat cells results in a net decrease of cellular sphingomyelin content. Among the products generated by the catabolism of sphingomyelin, sphingosine displayed exactly the same effect as sphingomyelinase. Sphingosine decreases the cytosolic Ca2+ concentration in cells treated with CD3, thapsigargin, or ionomycin. Studying the effect of sphingosine in CD3-activated cells showed that this compound does not modify Ca2+ mobilization from intracellular stores but strongly inhibited the Ca2+ influx induced by the monoclonal antibody. The fact that sphingosine inhibits Ca2+ influx generated by thapsigargin and ionomycin supports the hypothesis that the drug activates the Ca2+ extrusion process. Derivatives of sphingosine such as erythrosphinganine and threosphinganine share the same inhibitory properties.
Breittmayer
J P
JP
Laboratoire des Interactions Cellulaires et Moleculaires en Immunologie, Institut National de la Santé et de la Recherche Médicale U343, Faculté de Médecine, Nice, France.
Bernard
A
A
Aussel
C
C
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology*; D017252:CD3 Complex / Q000276:immunology / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D002460:Cell Line; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology*; D007700:Kinetics; D013108:Sphingomyelin Phosphodiesterase / Q000494:pharmacology*; D013110:Sphingosine / Q000494:pharmacology*; D013601:T-Lymphocytes; D013729:Terpenes / Q000494:pharmacology*; D019284:Thapsigargin; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D017252:CD3 Complex; D013729:Terpenes; D015759:Ionomycin; D019284:Thapsigargin; D013108:Sphingomyelin Phosphodiesterase; D000252:Calcium-Transporting ATPases; D013110:Sphingosine; D002118:Calcium