Experimental Studies Of The Expression Of Scavenger Receptor And CD14 In Trauma And Traumatic Endotoxemia And The Anti-infection Effect Of Carboxymethyl-β-1, 3-glucan

In recent years,the mechanism of sepsis,especially the receptor mechanism of the disequilibrium of pro- and anti- inflammatory response during the course of infection has been paid close attention. Research now have indicated that Scavenger Receptor and CD14 play key roles in the clearance, inactivation of endotoxin and activation of macrophages by endotoxin differently. The changes of them have intrinsic relationship with local pro- and anti- inflammation, tissue injury and organ dysfunction. The study was performed as the following four aspects: 1. to explore the dynamic expression of SR and CD14 after trauma and traumatic endotoxin challenge. Their differences of organic distribution are also analyzed; 2. to explore the dynamic expression of SR and CD14 on alveolar macrophages after trauma and traumatic endotoxin challenge and its significance; 3. to explore the effect of carboxymethyl-β-1,3-glucan, an potent immunomodulator, on the expression of SR on alveolar macrophages and their function; 4. to explore the effect of carboxymethyl-β-1,3-glucan on the lung and the liver injury and mortality of traumatic endotoxin challenge animals, so as to further disclose the expression of SR and CD14 on the liver and lung macrophages for the analysis of injury difference on the liver and the lung. By the observance of protective effect on traumatic endotoxin animals, it is possible to further elucidate the mechanism of uncontrolled inflammation in sepsis and to provide experimental evidence for its effective prophylaxis and therapeutic method.The main results are as follows:1. The results indicated after trauma, the expression of CD14 and SR on macrophages of liver showed the tendency of up- and down-regulation respectively in 9 h, while the expression of CD14 and SR on macrophages of lung showed the tendency of up- and down-regulation respectively in 6 h, Furthermore, post-traumatic endotoxin challenge induces CD14 up-regulation and SR down-regulation drastically in 2 h after trauma. Correlation analysis indicated that CD14 and SR have significantly negative relationship both in liver and lung, and there exists some differences between liver and lung on kinetics of CD14 and SR. 2. The study showed 6 h after trauma, the expression of CD14 and SR on AM showed the tendency of up- and down-regulation respectively. Post- traumatic endotoxin challenge induces CD14 up-regulation and SR down- regulation drastically,which is similar to those of the lung tissue. 3. Carboxymethyl-β-1,3-glucan obviously inhibited the down regulation of SR on AM induced by LPS, which showed the time- and dose-dependent manner. Also, it significantly increased the opsonin-independent phagocytosis of Staphylococcus. aureus, which is inhibited by SR mono-antibody.4. The study found CMG can also mitigate the lung and the liver injury, decreasing the mortality of traumatic endotoxin challenge animals. Conclusions:1. After trauma, the expression of SR and CD14 in the liver and the lung tissue or on AM changes to some extent. After traumatic endotoxin challenge, the down-regulation of SR and the up-regulation of CD14 are more significant than those in trauma.2. The expression of SR and CD14 in the liver and the lung showed intrinsic correlation with local inflammatory disequilibrium and organ injury. The two-side modulation of CD14 and SR may be a vital reason of the tissuemacrophages' transformation from defence cells to effect ones.3. After traumatic endotoxin challenge, there exist some differences on the range of dynamic changes of SR and CD14, the changes in the lung tissue is even more obvious. These differences may be related to the sequential injury of liver and lung.4. CMG can strengthen the nonspecific defensive function of AM and alleviate their excessive activation by increasing the LPS clearance induced by SR. So, it's probably a promising immunomodulator in sepsis therapy.