Effect Of Immune Complexes On Monocyte-Macrophage And Mechanism

BackgroundSystemic lupus erythematosus (SLE) is a multi-system organ involvement, especially skin and kidney,chronic progressive autoimmune disease, the emergence of a variety of auto-antibodies include anti-nuclear antibody as the main pathologic features. Autoantigen-associated protein and nuclear acids(DNA and RNA) and autoantibody form the circulating immune complexes, Immune complexes deposit in tissues and organs and cause inflammatory response to damage the corresponding organ constitute to the immune pathologic basis..The pathogenesis of SLE remains unknown. The interactions between genetic susceptibilities and various environmental factors (virus infection, hormone abnormality, and so on) may contribute to the immune dysfunction of SLE patients. Several immune dysfunctions play important roles in SLE. The abnormal activation of autoreactive T and B lymphocyte result in the production of autoantibodies. The decreased capability of the negative-regulated function to immune reaction of inhibitory immunocytes leads to the overreaction of immune effector cells. Excessive secretion of a number of proimflammatory cytokines, such as tumor necrosis factor-a (TNF-a) and B-cell-activating factor (BAFF), may exacerbate the imflammation of SLE patients. BAFF is a key factor during B cell maturation and B cell tolerance development. Once adjustment balance of BAFF expression is destroyed, it results in excessive BAFF production that impairs B cell tolerance and leads to autoimmune phenomena. However, most sources of cytokines is not clear. High mobility group box 1 (HMGB1)is a nuclear protein concerning with chromatin construction and transcriptional regulation..HMGB1 can bind DNA in a non-sequence-specific way and interact with nuclear protein.Elevated levels of HMGB1 were found in the sera of SLE patients and mice with lupus-like disease. The receptor for advanced glycation end products (RAGE) is thought to be one of the important receptors mediating HMGB1 signaling. The HMGB1-RAGE interaction promotes chemotaxis and maturation of immune cells, enhances the expression of adhesion molecules in endothelial cells, and stimulates the production of cytokines by various types of cells.Monocytes/macrophages are important human immune cells, in the innate immune response play an important role, but also to participate in specific immune response The hallmark function of the monocytes/macrophages system is phagocytosis and subsequent antigen presentation monocytes/macrophages through phagocytosis of foreign body, bacteria, aging and mutation of cells and immune complexes to maintain the immune homeostasis. At the same time, activation of monocytes/macrophages can secrete a large number of chemokines and cytokines, involved in the body natural and acquired immune regulation. Many studies have prove that monocytes/macrophages dysfunction. Data derived from animal studies regarding the central role of monocytes/macrophages in systemic autoimmunity propose that the monocytes/macrophages pathogenesis in SLE is defective.Objective:To study the immune complexes on monocyte-macrophage cell proliferation, cytokine secretion and regulation of phagocytic function and mechanism.Methods:The immune complex (cell necrosis supernatant+SLE serum) and the corresponding control group (necrosis supernatant+normal human serum, necrosis supernatant group, SLE serum group, normal serum group and medium group) were applied to U937 cells and U937 cells were induced macrophages.24 hours later, CCK-8 was detected with the U937 cell proliferation; RT-PCR Detection of U937 cells to secrete TNF, BAFF cytokines, such as changes; neutral red colorimetric assay after induction of the macrophage. RAGE antibody blocked experimental study mechanism of action.Results:The immune complex can promote the proliferation of U937 cells to TNF, BAFF secretion of cytokines, such as an increase, inhibit macrophage phagocytosis, anti-RAGE antibody antagonist immune complexes on monocyte-macrophage cells in the above-mentioned effect.Conclusion:The immune complexes through the RAGE pathway may promote monocyte-macrophage cell proliferation, increased cytokine secretion, inhibit phagocytosis, involved in the occurrence and development of systemic lupus erythematosus...