Abstract
The Tn antigen, an N-acetylgalactosamine structure linked to serine or threonine, has been shown to induce high-specificity, high-affinity anti-Tn antibodies in mice. Maternal immunization with the Tn vaccine increases serum anti-Tn antibody titers and attenuates hyperoxia-induced kidney injury in neonatal rats. However, immunizing mothers to treat neonatal kidney disease is clinically impractical. This study is aimed at determining whether anti-Tn monoclonal antibody treatment ameliorates hyperoxia-induced kidney injury in neonatal mice. Newborn BALB/c mice were exposed to room air (RA) or normobaric hyperoxia (85% O2) for 1 week. On postnatal days 2, 4, and 6, the mice were injected intraperitoneally with PBS alone or with anti-Tn monoclonal antibodies at 25 μg/g body weight in 50 μL phosphate-buffered saline (PBS). The mice were divided into four study groups: RA + PBS, RA + anti-Tn monoclonal antibody, O2 + PBS, and O2 + anti-Tn monoclonal antibody. The kidneys were excised for histology, oxidative stress, cytokine, and Western blot analyses on postnatal day 7. The O2 + PBS mice exhibited significantly higher kidney injury scores, 8-hydroxy-2'-deoxyguanosine (8-OHdG) and nuclear factor-κB (NF-κB) expression, and cytokine levels than did the RA + PBS mice or RA + anti-Tn mice. Anti-Tn monoclonal antibody treatment reduced kidney injury and cytokine levels to normoxic levels. The attenuation of kidney injury was accompanied by a reduction of oxidative stress and NF-κB expression. Therefore, we propose that anti-Tn monoclonal antibody treatment ameliorates hyperoxia-induced kidney injury by suppressing oxidative stress and inflammation in neonatal mice.
Highlights
Supplemental oxygen is often required to treat newborns with respiratory disorders
Our in vivo model demonstrated that hyperoxia exposure during the first 7 days after birth induced kidney injury, as demonstrated by increased kidney injury scores and cytokine levels
The improvement of kidney injury was associated with a reduction in oxidative stress, nuclear factor-κB (NF-κB) expression, and cytokine levels
Summary
Administering highconcentration oxygen to newborn infants with respiratory failure increases oxidative stress and leads to kidney injury [1]. Prolonged hyperoxia induces glomerular and tubular damage in neonatal rodents, which manifests as enlarged renal corpuscles, renal tubular necrosis, interstitial inflammation, and kidney fibrosis during the perinatal period [2,3,4,5,6]. These harmful effects may continue into adulthood [4, 7]. Chiang et al used linear array epitope technology to develop an anti-Tn vaccine that induces high-specificity, high-affinity anti-Tn antibodies in mice
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