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Updated: Aug 8, 2026
A Controlled Mouse Model for Neonatal Polymicrobial Sepsis
Published on: January 27, 2019
Sepsis-induced alteration in T-cell Ca(2+) signaling in neonatal rats
M H Alattar1, T M Ravindranath, M A Choudhry
1Burn and Shock Trauma Institute, Loyola University Medical Center, 2160 South First Avenue, Maywood, IL 60153, USA.
Abstract:
Sepsis-induced suppression in T-cell proliferation follows deranged Ca(2+) signaling in adult rats. In preliminary studies, we observed suppression in T-cell proliferation in septic neonatal rats as well. In this study, we assessed splenic T-cell cytosolic Ca(2+) concentration, [Ca(2+)](i), as its elevation plays an important role in T-cell proliferation. Also, we investigated the role of PGE(2) in sepsis-related changes in T-cell [Ca(2+)](i) in animals pretreated with cyclooxygenase-1 (COX-1) inhibitor (resveratrol) and cyclooxygenase-2 (COX-2) inhibitor (NS-398). Sepsis was induced in 15-day-old rat pups by intraperitoneal implantation of fecal pellets containing Escherichia coli and Bacteroides fragilis. The sham group consisted of pups implanted with sterile fecal pellets. Septic and sham pups were sacrificed 24 h after implantation and their spleens were removed. The spleens from sham and septic pups, along with spleens from unoperated control pups, were processed for single cell suspensions, and T cells were isolated using nylon wool columns. Fura-2 fluorophotometry was employed for the measurement of [Ca(2+)](i) (in nM units) in T cells stimulated with concanavalin A (ConA). Our results show that ConA-mediated T-cell [Ca(2+)](i) response is significantly suppressed in septic neonatal rats. Pretreatment of pups with COX-2, but not COX-1 inhibitor, prevented the decrease in the [Ca(2+)](i) response. These findings suggest that PGE(2) might induce the attenuation in T-cell Ca(2+) signaling during sepsis in neonatal rats.
Insights
Sepsis suppresses T-cell proliferation in neonatal rats by disrupting calcium signaling. Prostaglandin E2 (PGE2) plays a key role, with cyclooxygenase-2 (COX-2) inhibition protecting T-cell function.
Area of Science:
- Immunology
- Neonatal Sepsis Research
- Calcium Signaling
Background:
- Sepsis impairs T-cell proliferation, a critical immune response.
- Previous studies indicated T-cell dysfunction in septic adult rats.
- Neonatal sepsis also shows suppressed T-cell proliferation.
Purpose of the Study:
- To investigate sepsis-induced alterations in splenic T-cell cytosolic calcium concentration ([Ca(2+)](i)) in neonatal rats.
- To explore the role of prostaglandin E2 (PGE2) in sepsis-related changes in T-cell [Ca(2+)](i).
- To assess the impact of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) inhibition on T-cell calcium signaling during neonatal sepsis.
Main Methods:
- Sepsis was induced in 15-day-old rat pups using fecal pellets.
- T-cells were isolated from spleens of septic, sham, and control pups.
- Fura-2 fluorophotometry measured T-cell [Ca(2+)](i) responses to concanavalin A (ConA) stimulation.
- Animals were pretreated with COX-1 (resveratrol) or COX-2 (NS-398) inhibitors.
Main Results:
- ConA-mediated T-cell [Ca(2+)](i) response was significantly suppressed in septic neonatal rats.
- Pretreatment with a COX-2 inhibitor, but not a COX-1 inhibitor, prevented this suppression.
- These findings implicate PGE2 in the T-cell calcium signaling deficits observed during neonatal sepsis.
Conclusions:
- Neonatal sepsis significantly impairs T-cell calcium signaling.
- PGE2, mediated by COX-2, contributes to the suppression of T-cell calcium responses during sepsis.
- Targeting COX-2 may offer a therapeutic strategy to restore T-cell function in neonatal sepsis.
