Ce Yang1, Jie Gao, Hong Dong, Pei-Fang Zhu, Zheng-Guo Wang, Jian-Xin Jiang. 1. State Key Laboratory of Trauma, Burns and Combined Injury, Department 4, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
Abstract
BACKGROUND: Previous studies in our laboratory have demonstrated the downregulation of surface expression of scavenger receptor (SR) and upregulation of CD14 in the presence of endotoxemia, which directly correlates to the excessive inflammatory response in lung injuries. This study aims to analyze the dynamics of the expressions of SR and CD14 in traumatic endotoxemia, and to investigate the receptor mechanism of immunomodulator, carboxymethyl-beta-1, 3-glucan (CMG), on the protection of traumatic infections. METHODS: By using a sublethal fracture plus endotoxemia model, experimental mice were assigned to sham group (Sham), trauma group (T), traumatic endotoxemia group (TE), and traumatic endotoxemia plus CMG group (TE + C). Alveolar macrophages were isolated from each group. Expressions of SR and CD14 were examined at the cell and tissue levels by immunohistochemistry assay. The effects of CMG on the phagocytosis of alveolar macrophages, tissue injury, and mortality were also determined. RESULTS: Expressions of SR and CD14 in lungs and livers decreased and increased, respectively. Alteration of SR and CD14 levels was more evident in lungs than in livers in posttraumatic endotoxemia. CMG up-regulated the SR expression in lipopolysaccharide-stimulated alveolar macrophages, alleviated the tissue injury, reduced mice mortality, and increased the opsonin-independent phagocytosis of Staphylococcus aureus, which was inhibited by SR mono-antibody. CONCLUSION: Significant correlation was found between inflammatory responses and the imbalance between SR and CD14 in posttraumatic endotoxemia. The more dramatic changes in lungs might be related to the sequential preferred injury in uncontrolled inflammation. CMG could be a promising bioactive reagent in immunomodulating sepsis.
BACKGROUND: Previous studies in our laboratory have demonstrated the downregulation of surface expression of scavenger receptor (SR) and upregulation of CD14 in the presence of endotoxemia, which directly correlates to the excessive inflammatory response in lung injuries. This study aims to analyze the dynamics of the expressions of SR and CD14 in traumatic endotoxemia, and to investigate the receptor mechanism of immunomodulator, carboxymethyl-beta-1, 3-glucan (CMG), on the protection of traumatic infections. METHODS: By using a sublethal fracture plus endotoxemia model, experimental mice were assigned to sham group (Sham), trauma group (T), traumatic endotoxemia group (TE), and traumatic endotoxemia plus CMG group (TE + C). Alveolar macrophages were isolated from each group. Expressions of SR and CD14 were examined at the cell and tissue levels by immunohistochemistry assay. The effects of CMG on the phagocytosis of alveolar macrophages, tissue injury, and mortality were also determined. RESULTS: Expressions of SR and CD14 in lungs and livers decreased and increased, respectively. Alteration of SR and CD14 levels was more evident in lungs than in livers in posttraumatic endotoxemia. CMG up-regulated the SR expression in lipopolysaccharide-stimulated alveolar macrophages, alleviated the tissue injury, reduced mice mortality, and increased the opsonin-independent phagocytosis of Staphylococcus aureus, which was inhibited by SR mono-antibody. CONCLUSION: Significant correlation was found between inflammatory responses and the imbalance between SR and CD14 in posttraumatic endotoxemia. The more dramatic changes in lungs might be related to the sequential preferred injury in uncontrolled inflammation. CMG could be a promising bioactive reagent in immunomodulating sepsis.
Authors: Tammy R Ozment; Tuanzhu Ha; Kevin F Breuel; Tiffany R Ford; Donald A Ferguson; John Kalbfleisch; John B Schweitzer; Jim L Kelley; Chuanfu Li; David L Williams Journal: PLoS Pathog Date: 2012-10-11 Impact factor: 6.823