CD3 monoclonal antibodies evoke the same cytochrome P450-regulated capacitative entry of calcium as thapsigargin in Jurkat T cells.
In T cells CD3 monoclonal antibodies mediate an elevation of cytosolic Ca2+ concentration due to a release from internal stores and also due to an entry from extracellular medium, the mechanism of which is not clearly elucidated. Previous studies on several cell types have reported that depleting intracellular Ca2+ stores with inhibitors of the reticulum Ca(2+)-ATPase resulted in an increased plasma membrane permeability to calcium ions. It has been suggested that emptying the reticulum triggers a Ca2+ influx from extracellular medium, independent of phosphoinositide hydrolysis. To document the physiological relevance of such a mechanism, we compared CD3- and thapsigargin-induced sustained increase of cytosolic Ca2+ concentration in Jurkat T cells with regard to their sensitivity to internal and external Ca2+ level and to several inhibitors which do not affect the release of internal stores. We show that (1) there was no additivity of the two effects; (2) both CD3- and thapsigargin-evoked Ca2+ influx were inhibited when membrane was depolarized by either gramicidin or a high potassium concentration; and (3) Ca2+ influx was abrogated by cytochrome P450 inhibitors such as lipoxygenase inhibitors or imidazole antimicotic drugs. CD3 mAb and thapsigargin thus triggered the same signaling events, probably involving a cytochrome P450, to transmit information from depleted endoplasmic reticulum to the plasma membrane.
Breittmayer
J P
JP
INSERM U343, Faculté de Médecine, Nice, France.
Berthe
P
P
Cousin
J L
JL
Bernard
A
A
Aussel
C
C
D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D003022:Clotrimazole / Q000494:pharmacology; D004464:Econazole / Q000494:pharmacology; D006801:Humans; D007211:Indoles; D007213:Indomethacin / Q000494:pharmacology; D009637:Masoprocol / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D016853:Muromonab-CD3 / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D013729:Terpenes / Q000494:pharmacology*; D019284:Thapsigargin
D007211:Indoles; D016853:Muromonab-CD3; D013729:Terpenes; D019284:Thapsigargin; D004464:Econazole; D009637:Masoprocol; D003022:Clotrimazole; C048960:indo-1; D002118:Calcium; D007213:Indomethacin