Sepsis-induced alteration in T-cell Ca2+ signaling in neonatal rats

Sepsis-induced suppression in T-cell proliferation follows deranged Ca2+ si gnaling in adult rats. In preliminary studies, we observed suppression in T -cell proliferation in septic neonatal rats as well. In this study, we asse ssed splenic T-cell cytosolic Ca2+ concentration, [Ca2+](i), as its elevati on plays an important role in T-cell proliferation. Also, we investigated t he role of PGE(2) in sepsis-related changes in T-cell [Ca2+](i) in animals pretreated with cyclooxygenase-1 (COX-1) inhibitor (resveratrol) and cycloo xygenase-2 (COX-2) inhibitor (NS-398). Sepsis was induced in 15-day-old rat pups by intraperitoneal implantation of fecal pellets containing Escherich ia coli and Bacteroides fragilis. The sham group consisted of pups implante d with sterile fecal pellets. Septic and sham pups were sacrificed 24 h aft er implantation and their spleens were removed. The spleens from sham and s eptic pups, along with spleens from unoperated control pups, were processed for single cell suspensions, and T cells were isolated using nylon wool co lumns. Fura-2 fluorophotometry was employed for the measurement of [Ca2+], (in nM units) in T cells stimulated with concanavalin A (ConA). Our results show that ConA-mediated T-cell [Ca2+](i) response is significantly suppres sed in septic neonatal rats. Pretreatment of pups with COX-2, but not COX-1 inhibitor, prevented the decrease in the [Ca2+](i) response. These finding s suggest that PGE(2) might induce the attenuation in T-cell Ca2+ signaling during sepsis in neonatal rats. Copyright (C) 2001 S. Karger AG, Basel.