The Difference Of Toll-like Receptor 4 Expression On Alveolar And Interstitial Macrophages In Severe Thoracic Trauma

Acute lung injury (ALI) is a common complication of severe thoracic trauma, and it may lead to the development of acute respiratory distress syndrome (ARDS). Though ARDS has been studying for more than 30 years, the mechanism about its development is not well understood, and its mortality is still about 50-60%. So, the study on ARDS is an urgent subject in trauma research and clinic practice.After severe thoracic trauma, lots of pro- and anti-mediators of inflammation pour in the blood, they evoke excessive inflammatory responses and inhibit the immunity, serious infection may develop due to these disorders, and macrophages in lungs play an important role in the occurring of these pathological changes. Macrophages is the resident of lungs and it is the first line of defence against pathogenic microorganism, it is crucial for the startup of innate and acquired immunity. Macrophages from different subgroup play different roles in the immune disorders after trauma. Many researches found that the alveolar macrophages (AM) and interstitial macrophages (IM) show heterogeneity, they have different functions in the immune response.Our previous research showed that severe thoracic trauma could increase LPS, Toll-like receptor 4 (TLR4), a member of the Toll family was found recently, and it is considered to be an important factor in the pathway for the signal transduction of LPS in cells; The signal transduction promoted by TLR4 can activate NF-kB, and make monocytes and macrophages produce inflammatory cytokines, costimulatory molecules, or magnify the non-specified immune response. So TLR4 is an extremely important innate immune receptor. To study the role of TLR4 in the development of ALI is promising, it will provide valuable knowledge for the study of immune disorder after trauma and the prevention and treatment of its complications.Based on the above knowledge, the present research established a rat model of severe thoracic trauma, AM and EVI were collected by mechanic flush and enzymatic digestion,and the following studies were done: the morphological compare of AM and IM; changes of the phagocytosis, angtigen presentation and secretion of AM and EM after trauma were observed dynamically; at the mean time, the level of AM and EM TLR4-mRNA and the expression of TLR4 protein was measured by Northern and Western blot. Following results and conclusion were made from the research:1, a stable and reliable severe thoracic trauma model was successfully established with 400Kpa-strike on the up-right chest of rat by a multiple-function strike apparatus .2, highly purified AM and EM were obtained by flush of trachea, bronchia, blood bed and enzymatic digestion. It is important for the further investigation.3, there were significant morphological difference between AM and EM.4, the phagocytosis of AM was stronger than EM, the LPS due to trauma had a biphasic effects on the phagocytosis of AM and EM, firstly enhanced then inhibited. The antigen-presentation of EM was stronger than AM, and LPS inhibited this function in both AM and EM. AM secreted more TNF-a than EM, EM secreted more EL-6 than AM, LPS increased the secretion of both AM and EM. AM and EM had heterogeneity, they showed different effects on the immune disorders after trauma, and EM could not be simply regarded as the precursor to AM.5, there was a basic expression of TLR4 in AM and EM, the levels of the expression were not the same; the expression could be up-regulated by trauma and the highest expression of AM occurred 8 hours, EM occurred 8,16 hours after the occurring of trauma, the up-regulation of TLR-4 participated in the pathological procedure of excessive inflammation.The present study provided valuable laboratorial and theoretical evidence for the research on ALI complicated with severe thoracic trauma.