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J. Biol. Chem., Vol. 276, Issue 20, 17568-17575, May 18, 2001
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From the In this study
arachidonate-phospholipid remodeling was investigated in resting and
proliferating human T lymphocytes. Lymphocytes induced to proliferate
with either the mitogen concanavalin A or with anti-CD3 (OKT3) in
combination with interleukin 2 (OKT3/IL-2) showed a greatly accelerated
rate of [3H]arachidonate-phospholipid remodeling
compared with resting lymphocytes or with lymphocytes stimulated with
OKT3 or IL-2 alone. The concanavalin A-stimulated cells showed a 2-fold
increase in the specific activity of CoA-independent transacylase
compared with unstimulated cells, indicating that this enzyme is
inducible. Stimulation with OKT3 resulted in greatly increased
quantities of the group VI calcium-independent phospholipase
A2 but not of the quantity of group IV cytosolic phospholipase A2. However, group IV phospholipase
A2 became phosphorylated in OKT3-stimulated cells, as
determined by decreased electrophoretic mobility. Incubation of cells
with the group VI phospholipase A2 inhibitor, bromoenol
lactone, or the dual group IV/group VI phospholipase A2
inhibitor, methyl arachidonyl fluorophosphonate, did not block
arachidonate-phospholipid remodeling resting or proliferating T cells,
suggesting that these phospholipases A2 were not involved
in arachidonate-phospholipid remodeling. The incubation of
nonproliferating human lymphocytes with inhibitors of CoA-independent
transacylase had little impact on cell survival. In contrast,
OKT3/IL-2-stimulated T lymphocytes were very sensitive to apoptosis
induced by CoA-independent transacylase inhibitors. Altogether these
results indicate that increased arachidonate-phospholipid remodeling is
associated with T cell proliferation and that CoA-independent transacylase may be a novel therapeutic target for proliferative disorders.
Anti-CD3 and Concanavalin A-induced Human T Cell
Proliferation Is Associated with an Increased Rate of
Arachidonate-Phospholipid Remodeling
LACK OF INVOLVEMENT OF GROUP IV AND GROUP VI PHOSPHOLIPASE
A2 IN REMODELING AND INCREASED SUSCEPTIBILITY OF
PROLIFERATING T CELLS TO CoA-INDEPENDENT TRANSACYLASE INHIBITOR-INDUCED
APOPTOSIS*
and
§¶
Centre de Recherche en Rhumatologie et
Immunologie, Centre de Recherche du Centre Hospitalier Universitaire de
Québec, Pavillon CHUL and Faculté de Médecine,
Université Laval, Québec G1V 4G2, Canada and
§ Pilot Therapeutics Inc.,
Winston-Salem, North Carolina 27101
*
These studies were supported by a grant from the Medical
Research Council of Canada and were presented in part at the 6th International Conference on Eicosanoids and Other Bioactive Lipids in
Cancer, Inflammation-related Diseases, Boston, MA, September 12-15,
1999.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
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