TY - JOUR

T1 - Ca2+ influx in human T lymphocytes is induced independently of inositol phosphate production by mobilization of intracellular Ca2+ stores. A study with the Ca2+ endoplasmic reticulum‐ATPase inhibitor thapsigargin

AU - Gouy, Hélène

AU - Cefai, Daniel

AU - Christensen, Soren Brogger

AU - Debré, Patrice

AU - Bismuth, Georges

PY - 1990/10

Y1 - 1990/10

N2 - Thapsigargin (TG), a sesquiterpene lactone and non‐phorbol 12‐myristate 13‐acetate tumor promoter, stimulates a rapid increase in intracellular free Ca2+ ([Ca2+]i) in human T lymphocytes clone P28. The [Ca2+]i response to TG is sustained in the presence of 1 mM extracellular Ca2+, while it becomes transient in Ca2+‐free medium suggesting that TG activates both the release of Ca2+ from intracellular stores and the entry of Ca2+ from extracellular spaces. TG‐induced Ca2+ influx is completely abolished after cell depolarization caused by increased extracellular concentrations of K+. The rise in [Ca2+]i stimulated by TG occurs in the absence of detectable production of inositol phosphates. Moreover, TG does not alter the early biochemical events of T cell activation triggered through the CD2 or the CD3 T cell antigens. Indeed, both inositol phosphate production and intracellular pH increase induced by specific monoclonal antibodies (mAb) remain unchanged after TG treatment. These data suggest that in human T lymphocytes TG releases Ca2+ from an intracellular pool by a mechanism which is independent of the phospholipase C metabolic pathway. Preincubation with TG of T cell clone P28 empties both the CD2 and the CD3‐sensitive intracellular Ca2+ pool(s). Conversely, prestimulation of T cell clone P28 by CD3 or CD2‐specific mAb inhibits the Ca2+‐mobilizing effect of TG. Thus it appears that TG and CD2‐or CD3‐specific mAb mobilize Ca2+ from common Ca2+ pool(s). Taken together, these results demonstrate that Ca2+ influx in human T cells may be linked to mobilization of intracellular Ca2+ pools and by a mechanism independent of phosphoinositide hydrolysis. They further indicate that the release of intracellular Ca2+ pool(s) may play a major role in the opening of cell membrane Ca2+ channels observed during the CD2‐ or CD3‐induced stimulation of human T lymphocytes.

AB - Thapsigargin (TG), a sesquiterpene lactone and non‐phorbol 12‐myristate 13‐acetate tumor promoter, stimulates a rapid increase in intracellular free Ca2+ ([Ca2+]i) in human T lymphocytes clone P28. The [Ca2+]i response to TG is sustained in the presence of 1 mM extracellular Ca2+, while it becomes transient in Ca2+‐free medium suggesting that TG activates both the release of Ca2+ from intracellular stores and the entry of Ca2+ from extracellular spaces. TG‐induced Ca2+ influx is completely abolished after cell depolarization caused by increased extracellular concentrations of K+. The rise in [Ca2+]i stimulated by TG occurs in the absence of detectable production of inositol phosphates. Moreover, TG does not alter the early biochemical events of T cell activation triggered through the CD2 or the CD3 T cell antigens. Indeed, both inositol phosphate production and intracellular pH increase induced by specific monoclonal antibodies (mAb) remain unchanged after TG treatment. These data suggest that in human T lymphocytes TG releases Ca2+ from an intracellular pool by a mechanism which is independent of the phospholipase C metabolic pathway. Preincubation with TG of T cell clone P28 empties both the CD2 and the CD3‐sensitive intracellular Ca2+ pool(s). Conversely, prestimulation of T cell clone P28 by CD3 or CD2‐specific mAb inhibits the Ca2+‐mobilizing effect of TG. Thus it appears that TG and CD2‐or CD3‐specific mAb mobilize Ca2+ from common Ca2+ pool(s). Taken together, these results demonstrate that Ca2+ influx in human T cells may be linked to mobilization of intracellular Ca2+ pools and by a mechanism independent of phosphoinositide hydrolysis. They further indicate that the release of intracellular Ca2+ pool(s) may play a major role in the opening of cell membrane Ca2+ channels observed during the CD2‐ or CD3‐induced stimulation of human T lymphocytes.

UR - http://www.scopus.com/inward/record.url?scp=0025196069&partnerID=8YFLogxK

U2 - 10.1002/eji.1830201016

DO - 10.1002/eji.1830201016

M3 - Journal article

C2 - 1700752

AN - SCOPUS:0025196069

VL - 20

SP - 2269

EP - 2275

JO - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

IS - 10

ER -