Expressions of scavenger receptor, CD14 and protective mechanisms of carboxymethyl-beta-1, 3-glucan in posttraumatic endotoxemia in mice.
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.


CONCLUSIONS
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.
Yang
Ce
C
State Key Laboratory of Trauma, Burns and Combined Injury, Department 4, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
Gao
Jie
J
Dong
Hong
H
Zhu
Pei-Fang
PF
Wang
Zheng-Guo
ZG
Jiang
Jian-Xin
JX
D000818:Animals; D019446:Endotoxemia / Q000276:immunology* / Q000473:pathology; D004926:Escherichia coli / Q000276:immunology*; D005260:Female; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008099:Liver / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D010587:Phagocytosis / Q000187:drug effects*; D051116:Receptors, Scavenger / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects; D014947:Wounds and Injuries / Q000276:immunology* / Q000473:pathology; D047071:beta-Glucans / Q000494:pharmacology*
D018950:Lipopolysaccharide Receptors; D051116:Receptors, Scavenger; D047071:beta-Glucans; C029933:carboxymethyl-beta-1,3-glucan