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PGE2 suppresses mitogen-induced Ca2+ mobilization in T cells
M A Choudhry1, P E Hockberger, M M Sayeed
1Trauma/Critical Care Research Laboratories, Departments of Surgery and Physiology, Burn & Shock Trauma Institute, Loyola University Chicago Medical Center, Maywood, Illinois 60153, USA.
Abstract:
PGE2-mediated suppression of T cell proliferation during sepsis could result from altered Ca2+ signaling. The present study evaluated the effects of PGE2 on Ca2+ release from intracellular stores and its influx through the plasma membrane in splenic T cells from Sprague-Dawley rats. Intracellular Ca2+ concentration ([Ca2+]i) responses in individual T cells were assessed using the Ca2+ imaging technique, and the release of Ca2+ from intracellular stores and Ca2+ influx were spectrofluorometrically quantified in T cell suspensions. Under unstimulated conditions, nearly 85% of T cells exhibited [Ca2+]i
Insights
Prostaglandin E2 (PGE2) suppresses T cell responses during sepsis by disrupting calcium signaling. PGE2 inhibits both calcium release from stores and influx into T cells, impairing their function.
Area of Science:
- Immunology
- Cellular Physiology
- Pharmacology
Background:
- Sepsis can lead to T cell dysfunction, potentially mediated by Prostaglandin E2 (PGE2).
- Calcium (Ca2+) signaling is crucial for T cell activation and proliferation.
Purpose of the Study:
- To investigate the impact of PGE2 on intracellular Ca2+ release and influx in splenic T cells.
- To elucidate the role of Ca2+ signaling in PGE2-mediated T cell suppression during sepsis.
Main Methods:
- Utilized Ca2+ imaging techniques to assess intracellular Ca2+ concentration ([Ca2+]i) in individual T cells.
- Quantified Ca2+ release from intracellular stores and Ca2+ influx using spectrofluorometry in T cell suspensions.
- Stimulated T cells with concanavalin A (Con A) and evaluated the effects of PGE2 pretreatment.
Main Results:
- PGE2 did not affect basal [Ca2+]i in resting T cells but significantly suppressed Con A-induced [Ca2+]i elevation.
- Con A stimulation increased [Ca2+]i in approximately 60% of T cells.
- PGE2 inhibited both the early Ca2+ release from intracellular stores and the late phase of Ca2+ influx.
Conclusions:
- PGE2 suppresses T cell activation by disrupting Ca2+ signaling pathways.
- The inhibitory effect of PGE2 involves blunting both intracellular Ca2+ release and plasma membrane Ca2+ influx.
- These findings highlight a key mechanism of T cell suppression during sepsis.