IL-2-REGULATED EXPRESSION OF Na+,Ê+-ATPase IN ACTIVATED HUMAN
LYMPHOCYTES
I. A. Karitskaya,1 N. D. Aksenov, T. A. Vinogradova, 1.1. Marakhova
Institute of Cytology RAS, St. Petersburg, Russia;
1 e-mail: inkar@mail.cytspb.rssi.ru
Expression of Na+,Ê+-ATPase alfa1-subunit and of oubain-sensitive rubidium influxes has been
investigated in human peripheral blood lymphocytes. Isolated lymphocytes were stimulated by phytogemagglutinin (PHA) or interleukin-2
(IL-2). It has been shown that during the early stage of the PHA-activation the alfa1-subunit abundance in the membrane fractions of
the human blood lymphocytes does not change, whereas at the late stages of G0 -> G1 -> S transition (16-48 h)
the alfal protein content increases. A translation inhibitor cycloheximide was found to prevent the late increase in alfa1-subunit
expression. An immunosuppressant cyclosporin A decreases both IL-2-dependent T-lymphocyte progression and alfa1-subunit abundance
by 48 h of PHA-induced lymphocyte activation. In the lymphocytes pretreated by PHA in submitogenic concentration (0.8-1.0 μg/ml)
exogenous IL-2 (100 U/ml) induces a proliferative response as well as alfa1-protein accumulation. A decrease in alfa1-protein
accumulation in the presence of specific inhibitors of separate signal transducti-on pathways enables us to conclude that protein
kinases ERK1/2 (ÌÀÐÊ pathway) and JAK3 (JAK-STAT pathway) mediate the IL-2-dependent regulation of Na+,Ê+-ATPase
expression during lymphocyte transition from resting stage to proliferation. A correlation between changes in ouabain-sensitive
rubidium influxes and the alfal-subunit amount has been demonstrated. It is concluded that IL-2-dependent-progression of normal human
lymphocytes from quiescence to proliferation is accompanied by the increase in Na+,Ê+-ATPase alfa1-subunits
expression, and the enhanced transport activity of a sodium pump during the prereplicative stage is provided by the increased number
of functional pump units in plasma membrane.
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