Bilirubin impairs bactericidal activity of neutrophils through an antioxidant mechanism in vitro

Toshiyuki Arai, Yasunobu Yoshikai, Junichi Kamiya, Masato Nagino, Katsuhiko Uesaka, Norihiro Yuasa, Koji Oda, Tsuyoshi Sano, Yuji Nimura

    研究成果: ジャーナルへの寄稿記事

    28 引用 (Scopus)

    抜粋

    Background. Liver failure accompanied by hyperbilirubinemia after major hepatic resection is profoundly associated with septic complications. Although the immune dysfunction in cholestasis has been intensively investigated, the contribution of increased serum bilirubin to the impaired resistance to bacterial infection remains to be elucidated. Because bilirubin possesses an antioxidant activity, we hypothesized that bilirubin may scavenge reactive oxygen species (ROS) produced by neutrophils and consequently impair neutrophil bacterial killing. To address this, we evaluated the effects of bilirubin on the bactericidal activity of ROS or of neutrophils in vitro. Materials and methods. The antioxidant activity of bilirubin was determined using an ROS-sensitive fluorophore, dichlorofluorescin diacetate (DCFH-DA). Bilirubin concentration in the buffer solution was monitored spectorophotometrically after incubation with ROS. The effect of bilirubin on killing of Escherichia coli by ROS or by isolated human neutrophils was determined by counting the viable E. coli after incubation on nutrient agar. Results. The bilirubin concentration in the buffer solution was decreased by the addition of hydrogen peroxide, especially in the presence of peroxidase or ferrous iron. DCFH-DA oxidation by ROS or activated neutrophils was inhibited by bilirubin in a dose-dependent manner. The bactericidal activity of ROS or of isolated neutrophils was significantly attenuated by bilirubin. Conclusions. Bilirubin impairs bactericidal activity of neutrophils through scavenging ROS. Increased levels of serum bilirubin may well be responsible for the impaired bacterial clearance in patients with hyperbilirubinemia.

    元の言語英語
    ページ(範囲)107-113
    ページ数7
    ジャーナルJournal of Surgical Research
    96
    発行部数1
    DOI
    出版物ステータス出版済み - 1 1 2001

      フィンガープリント

    All Science Journal Classification (ASJC) codes

    • Surgery

    これを引用

    Arai, T., Yoshikai, Y., Kamiya, J., Nagino, M., Uesaka, K., Yuasa, N., ... Nimura, Y. (2001). Bilirubin impairs bactericidal activity of neutrophils through an antioxidant mechanism in vitro. Journal of Surgical Research, 96(1), 107-113. https://doi.org/10.1006/jsre.2000.6061