title: Grape seed proanthocyanidin extract protects lymphocytes against histone-induced apoptosis.
abstract: Apoptosis of lymphocytes is associated with immunosuppression and poor prognosis in sepsis. Our previous report showed that histones, nuclear proteins released from damaged or dying cells in sepsis, can mediate lymphocyte apoptosis via mitochondria damage. Grape seed proanthocyanidin extract (GSPE), a natural substance with protective properties against oxidative stress, plays a vital role in cell and mitochondria protection. We thus hypothesized that GSPE may play a protective role in histone-induced lymphocyte apoptosis through its anti-oxidative properties. In this study, we investigated the protective efficacy of GSPE on lymphocyte apoptosis induced by extracellular histones, a main contributor of death in sepsis. Human blood lymphocytes were treated with 50 μg/ml histones, 2 μg/ml GSPE, or a combination of both. A total of 100 μMN-acetylcysteine (NAC), a reactive oxygen species (ROS) inhibitor, was used as a positive control for GSPE. Apoptosis, intracellular ROS levels, mitochondrial membrane potential, Bcl-2 expression, and caspase-3 cleavage were measured. Our data clearly indicate that GSPE significantly inhibited lymphocyte apoptosis, generation of ROS, the loss of mitochondrial membrane potential, the decrease in Bcl-2 expression, and caspase-3 activation induced by extracellular histones. In conclusion, we show that GSPE has a protective effect on lymphocyte apoptosis induced by extracellular histones. This study suggests GSPE as a potential therapeutic agent that could help reduce lymphocyte apoptosis, and thus the state of immunosuppression was observed in septic patients.
authors.affiliation: Department of ICU, Zhujiang Hospital of Southern Medical University , Guangzhou, Guangdong , China.
authors.forename: Ping
authors.initials: P
authors.lastname: Chang
authors.affiliation: Department of ICU, Zhujiang Hospital of Southern Medical University , Guangzhou, Guangdong , China.
authors.forename: Bing
authors.initials: B
authors.lastname: Mo
authors.affiliation: Department of Surgery, University of California San Diego , La Jolla, CA , USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Cauvi
authors.affiliation: Department of ICU, Zhujiang Hospital of Southern Medical University , Guangzhou, Guangdong , China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of MICU, General Hospital of Guangzhou Military Command , Guangzhou, Guangdong , China.
authors.forename: Zhenhui
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of ICU, Zhujiang Hospital of Southern Medical University , Guangzhou, Guangdong , China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of ICU, Zhujiang Hospital of Southern Medical University , Guangzhou, Guangdong , China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department of MICU, General Hospital of Guangzhou Military Command , Guangzhou, Guangdong , China.
authors.forename: Qitao
authors.initials: Q
authors.lastname: Yan
authors.affiliation: Department of ICU, Zhujiang Hospital of Southern Medical University , Guangzhou, Guangdong , China.
authors.forename: Guiming
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of ICU, Zhujiang Hospital of Southern Medical University , Guangzhou, Guangdong , China.
authors.forename: Zhanguo
authors.initials: Z
authors.lastname: Liu
keywords: Grape seed proanthocyanidin extract; Histones; Lymphocyte apoptosis; Mitochondrial injury; Reactive oxygen species