Role of Annexin II on the Cell Migration and Phagocytosis of Apoptotic Cells by Macrophages:Study on the Pathological Effects of Antibodies against SARS-Coronavirus Spike Protein Domain 2

• Main Authors: Chang-Yao Chaing, 江承堯
• Other Authors: Yee-Shin Lin
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/64907482545752263982

碩士 === 國立成功大學 === 微生物及免疫學研究所 === 94 === Apoptotic cell clearance by phagocytes is a homeostasis mechanism in human. Failure of phagocytes to uptake apoptotic cells may cause autoimmune disease. Pervious study in our laboratory showed that in SARS patient sera, there were autoantibodies that reacted with human lung epithelial cells. Preabsorption and binding assays indicated the existence of cross-reactive epitopes on SARS-CoV spike protein domain 2 (S2). Several candidate autoantigens have been identified. Among them, annexin II has been shown to play an important role in phagocytosis of apoptotic cells by macrophage. We hypothesize that anti-S2 antibody might bind to annexin II on macrophages and inhibit their phagocytic activity to apoptotic cells. Human monocytic cell lines THP-1 and U937 were activated by phorbol 12-myristate 13-acetate (PMA) for 24 to 96 h, which caused an increase in the annexin II expression. An increase in the ability of activated monocytic cells to phagocytose apoptotic cells was also observed. We showed anti-phagocytic effect of anti-S2 antibodies in PMA-activated U937 cells by caspase-3 activity detection and in mouse peritoneal macrophages by time-lapse microscopy. Furthermore, anti-S2 and anti-annexin II antibodies inhibited the migration of peritoneal macrophage. Anti-S2 and anti-annexin II antibodies inhibited the binding of apoptotic cells to PMA-activated U937 cells. We propose that the inhibition of migration and binding to apoptotic cells of macrophage is involved in the anti-phagocytic effect of anti-S2 antibody. The mechanism and signaling of anti-S2-mediated inhibitory effect on phagocytes need to be investigated. Moreover, whether the anti-phagocytic activity of anti-S2 antibodies plays a role in SARS immunopathologic mechanism remains unresolved.