EFFECTS OF TRAUMA ON IMMUNE CELL-FUNCTION - IMPAIRMENT OF INTRACELLULAR CALCIUM SIGNALING

Immunosuppression following injury influences infectious morbidity and mortality. Impaired T-cell activation conceding to inadequate antigen recognition contributes to this immunosuppression. Successful activat ion and proliferation of T-cells requires precisely specified levels o f intracellular calcium thresholds and peak signals. The purpose of th is study was to evaluate intracellular calcium signaling following inj ury. Hospitalized blunt and penetrating trauma patients in a Level I T rauma Center following injury and sepsis were tested for immune cell c alcium signaling. Peripheral blood mononuclear cells (PBMC) were isola ted and calcium signaling tested with Fura-2 AM. PBMC from trauma pati ents had significantly depressed values of baseline, peak and sustaine d levels of intracellular calcium prior to and following phytohemagglu tinin stimulation when compared to normal controls. This deficit in in tracellular calcium signaling is more severe in septic trauma patients (60% reduction). Suppression of calcium signaling appears to be media ted by at least, in part, circulating serum factors. Prostaglandin E(2 ) seems to have a limited contribution to this effect as it is suppres sive only when in direct contact with PBMC. Immune cell activation fai lure can in part be explained by the inadequacy of calcium signaling; restoration of immunocompetence following trauma will have to be addre ssed by strategies to restore calcium signaling, a vital step necessar y for T-cell proliferation following antigen recognition.