| Sepsis is a systemic inflammatory response syndrome (SIRS) associated with the presence of an infectious process caused by pathogenic microorganism or their toxin. It is one of the most common causes of morbidity and mortality in severe clinical patients who have a serious infection, trauma, shock, major operation, and so on. The fundamental pathogenesis and molecular mechanism of sepsis is very complex, including a number of problems, such as a variety of cell infection, inflammation, immune dysfunction, and coagulation dysfunction and tissue damage. Sepsis frequently progresses to septic shock and multiple organ dysfunction syndromes (MODS) which have a strong correlation with poor outcome.Lipopolysaccharide (LPS) is the major reason of sepsis. In the research of the pathogenesis in SIRS and sepsis, the second hit theory was accepted. First of all, LPS induces monocyte-macrophage cells to produce a variety of inflammatory mediators. Then, the inflammatory mediators further activate monocyte macrophages, endothelial cells, neutrophils, and other effector cells releasing more and more inflammatory mediators, leading to systemic inflammatory response. In the procedure of inflammatory reaction, LPS also activates endothelial cells and makes the coagulation and fibrinolytic system cascade activation, then promoting the deterioration of microcirculation. Therefore, if we make an in-depth study and effective intervention in the endothelial cells, it is expected to reduce the inflammation cascade. After endothelial cells were stimulated by LPS, some molecules in membrane of activated endothelial cells expose their active sites, or some molecules associated with pathological express increased, suggesting that the molecular structure and function are different between the stimulated cells and normal cells. These differential molecules probably are some important binding sites of inflammatory mediators in inflammatory cascade. Accordingly, if we can find the specific binding peptides of these differential molecules and competitive inhibit the combination of inflammatory mediators and effector cells, it would be possible to prevent or reduce the systemic inflammatory response.Cell is a complex biological system, its membrane distributs a large number of signal molecules, which reflect the characteristics and functional status of cells. Although these signal molecules can be purified to screening the specific binding peptides, but the purification is very difficult. It is better to use whole native cells to select the different molecules of the cell membrane on specific status without the information about the receptors. Whole-cell screening usually maintains the native conformation and biological activity of receptors. It can simulate the natural interaction between the protein molecules, and effectively find the specific marker proteins which are binding to the cell membrane. However, for the low antigen density of integrity cell membrane, it is difficult to screen by a single chain antibody. This screening method also presents a lot of disadvantages, such as high unspecificity, high background and losing specific ligands in the process of washing and so on.Fortunately, the phage display technique provides the approch to find the specific binding peptides of these differential molecules. In order to solve the problems above and get close to the in vivo environment as far as possible, we choosed a very elegant screening method to screening the specific binding peptides of human umbilical vein endothelial cells. The method, termed biopanning and rapid analysis of selective interactive ligands (BRASIL), was established by Giordano in 2001, and we have successfully completed the screening work of the subjects.In the process of analyzed these specific binding peptides, we have successfully set up a perfect and reliable bioinformatics analysis methods, and set it up a bioinformatics platform for internet user (http: //phdpap. fimmu.com).
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