Shimada Ken-ichi, Takimoto Hiroaki, Yano Ikuya, Kumazawa Yoshio
Department of Bioscience, School of Science, Kitasato University, Sagamihara, Kanagawa 228-8555, Japan.
Microbiol Immunol. 2006;50(3):243-51. doi: 10.1111/j.1348-0421.2006.tb03782.x.
We previously reported that glycopeptidolipid (GPL) isolated from Mycobacterium avium serovar 4 inhibited phagosome-lysosome (P-L) fusion when macrophages phagocytosed heat-killed Staphylococcus aureus (SA). In the present study we analyzed the underlying inhibitory mechanism of GPL coated on SA. Elimination of oligosaccharide from GPL abrogated its inhibitory activity. GPL did not inhibit P-L fusion of opsonized SA phagocytosed via complement receptors. The inhibitory activity of GPL was competitively reduced by the presence of alpha-methyl-D-mannoside and anti-mannose receptor antibody, suggesting that inhibition of P-L fusion by GPL is mediated through mannose receptor. Recruitment of early endosome antigen 1 and Ca2+/calmodulin kinase II in human macrophage-like THP-1 cells were significantly suppressed by GPL, indicating that GPL inhibits steps for leading to the P-L fusion.
我们之前报道过，从鸟分枝杆菌血清型4中分离出的糖肽脂（GPL）在巨噬细胞吞噬热灭活金黄色葡萄球菌（SA）时可抑制吞噬体-溶酶体（P-L）融合。在本研究中，我们分析了包被在SA上的GPL的潜在抑制机制。从GPL中去除寡糖消除了其抑制活性。GPL不抑制通过补体受体吞噬的调理素化SA的P-L融合。α-甲基-D-甘露糖苷和抗甘露糖受体抗体的存在竞争性地降低了GPL的抑制活性，这表明GPL对P-L融合的抑制是通过甘露糖受体介导的。GPL显著抑制人巨噬细胞样THP-1细胞中早期内体抗原1和Ca2+/钙调蛋白激酶II的募集，表明GPL抑制导致P-L融合的步骤。
