| Atherosclerosis is one of the most prevalent fatal diseases in the world, and results from an intricate interplay between diverse factors such as lipid metabolism, blood coagulation elements, cytokines, hemodynamic stress, and behavioral risk factors. Evidence suggesting the involvement of humoral and cellular immune reactions, at all stages of atherogenesis, has received scant attention for many years in classical atherosclerosis research. Moreover, increasing evidence shows that inflammatory and immunologic mediators may play a major role in the pathogenesis of atherosclerosis and coronary artery disease. There are many factors , such as the characterization of plaque, the numbers of smooth muscle cells and macrophages infiltration, which may contribute to the rupture and destabilization of the coronary plaque. However, it is unclear that what is the link or key factors for triggering the plaque rupture.The CD4O-CD4OL is a pair of type II membrane gtycoprotein with homology to tumor necrosis factor receptor(TNFR)family . The interaction of CD4O with CD4OL plays an important role of signal transduction pathway in humoral and cell-mediated immune responses. Gene mutations or abnormal expression of CD4O-CD4OL can lead to immunodeficiency and autoimmuney diseases. Recently, increasing amounts of evidence support the involvement of the CD4O-CD4OL receptor-ligand pair in atherogenesis. Most studies indicate that CD4OL activates atheroma-associated cells by promoting the expression of molecules thought to be involved in atherosclerosis, such as adhesion molecules, cytokines, matrix metalloproteinases, and tissue factor.It has been demonstrated that the formation and development of atherosclerosis5can be suppressed by prohibiting the interactions of CD4O and CD4OL in animal models. Thus, the expression of CD4O-CD4OL and its interaction might play a key role in the formation and development of AS. it is tempting to hypothesize that CD4O-CD4OL interaction may contribute to the development of atherosclerosis and promotion intracellular signal transduction pathway and increasingly leading to vicious circle and, by representing a new pathway of destabilization in human atheroma, also to the triggering of acute coronary events.In this study . The expression of CD4O and CD4OL were analyzed by RT-PCR, fluorescence microscope, flow cytometly and western blotting. Furthermore, immunohistochemistry technique was explored to analyze the expression of CD4O and CD4OL in the human aorta atheroma. Immunohistochemistry data suggested that CD4O and CD4OL protein expressed mainly in the plaque, with few in the other of the vascular wall. Ox-LDL and cytokines such as IL-i 1NF- T TNF can significantly increased the expression of CD4O and CD4OL both in HUVEC and monocytes.CD4OL can bind to HUVEC and monocytes by responding receptor and influence cellular signal transduction thereby such as DAG-PKC and calcium, DAG-PKC and Ca2~ is the important signal transduction links in cells . The levels of DAG were investigated with radioenzymatic assay, thin-layer chromatography and autoradiography. The activity of PKC was determined by its ability to transfer phosphate from [32P]ATP to tysine-rich histone and cytosolic free calcium [Ca2~]I was measured by flow cytometric analysis loading with the Ca2+ dye fluo3/Ani. The results showed that CD4OL not only induced a biphasic increase of DAG with an early transient phase peaking at 15 or 20 seconds and a late sustained phase peaking at 10 minutes , but also mediates CD4OL induced DAG elevation in a dose-dependent maimer in HUVEC and Mo . CD4OL increased PKC total activity in a dose-dependent manner and PKC activity was peak at 14 mm , the results also show that CD4OL induced PKC activity translocation from the cytosolic to membrane. Anti-CD4OMAb can significantly suppress DAG-PKC signal transduction pathway in both HVUEC and monocytes induced by rCD4OL.In this work, it was also showed that CD4OL induced biphasic [Ca2~]i responses6including the rapid initial t...
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