Ca(2+)-ATPase inhibitors induce interleukin-2 synthesis and T cell proliferation.

Abstract:

:In Jurkat cells, the three Ca(2+)-ATPase blockers, thapsigargin, cyclopiazonic acid, and di-tert-butylhydroquinone (DtBuHQ) induced both a release of Ca2+ from intracellular stores and a Ca2+ influx. In contrast to CD3 mAb, the Ca(2+)-ATPase inhibitors did not induce the formation of inositol trisphosphate from the hydrolysis of phosphatidylinositides. Emptying intracellular Ca2+ stores was accompanied by a decrease of phosphatidylserine (PtdSer) synthesis as previously observed in PHA- or CD3 mAb-treated Jurkat cells. In the presence of a phorbol ester able to activate protein kinase C, TPA, the three Ca(2+)-ATPase inhibitors induced Jurkat cells to synthesize large amounts of interleukin-2 demonstrating that early signal transduction mechanisms can be bypassed by Ca(2+)-ATPase inhibitors. In purified human peripheral blood T lymphocytes, the same inhibitors induced moderate if any cytosolic Ca2+ rise, in the absence of external calcium. Nevertheless analysis of PtdSer synthesis suggested that intracellular stores were efficiently depleted by DtBuHQ and cyclopiazonic acid but not by thapsigargin. In contrast, the three compounds induced similar Ca2+ influx. However, in the presence of TPA, cyclopiazonic acid and DtBuHQ induce highly purified T cells to proliferate while thapsigargin did not, suggesting that the status of internal Ca2+ store may have a decisive role in T cell activation.

journal_name

Cell Immunol

journal_title

Cellular immunology

authors

Breittmayer JP,Ticchioni M,Ferrua B,Bernard A,Aussel C

doi

10.1006/cimm.1993.1152

subject

Has Abstract

pub_date

1993-07-01 00:00:00

pages

248-57

issue

2

eissn

0008-8749

issn

1090-2163

pii

S0008-8749(83)71152-4

journal_volume

149

pub_type

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