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 activation and proliferation of T-cells requires precisely specified levels of intracellular calcium thresholds and peak signals. The purpose of this study was to evaluate intracellular calcium signaling following injury. Hospitalized blunt and penetrating trauma patients in a Level 1 Trauma Center following injury and sepsis were tested for immune cell calcium signaling. Peripheral blood mononuclear cells (PBMC) were isolated and calcium signaling tested with Fura-2 AM. PBMC from trauma patients had significantly depressed values of baseline, peak and sustained levels of intracellular calcium prior to and following phytohemagglutinin stimulation when compared to normal controls. This deficit in intracellular calcium signaling is more severe in septic trauma patients (60% reduction). Suppression of calcium signaling appears to be mediated by at least, in part, circulating serum factors. Prostaglandin E2 seems to have a limited contribution to this effect as it is suppressive only when in direct contact with PBMC. Immune cell activation failure can in part be explained by the inadequacy of calcium signaling; restoration of immunocompetence following trauma will have to be addressed by strategies to restore calcium signaling, a vital step necessary for T-cell proliferation following antigen recognition.
Hoyt
D B
DB
Department of Surgery, University of California San Diego 92103-8896, USA.
Junger
W G
WG
Loomis
W H
WH
Liu
F C
FC
D002118:Calcium / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology; D016257:Fura-2; D006801:Humans; D007165:Immunosuppression Therapy; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism*; D012774:Shock, Traumatic / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction
D015232:Dinoprostone; D002118:Calcium; D016257:Fura-2