Neill M A, Klebanoff S J
Department of Medicine, University of Washington, Seattle 98195.
J Exp Med. 1988 Jan 1;167(1):30-42. doi: 10.1084/jem.167.1.30.
Purified PGL-1 and dPGL from M. leprae can prevent bacterial killing by intact phagocytes and cell-free antimicrobial systems. Both glycolipids completely abolished the antimicrobial effect of the acetaldehyde-XO-Fe2+ system. Because the cytotoxicity of this system is inhibited by catalase, SOD, mannitol, and ethanol, but not by heated SOD or catalase, these data suggest that toxicity is due to OH. generated by the Haber-Weiss reaction. That the antimicrobial killing in the XO system is completely blocked by the addition of PGL-1 or dPGL suggests that these glycolipids can act as OH. scavengers. A modest protective effect against the cytotoxicity of the MPO-H2O2-halide system by both PGL-1 and dPGL was also observed. The antimicrobial activity of the MPO system was abolished with chloride, but not iodide, as the halide. The effect of the M. leprae-derived glycolipid on bacterial killing by intact phagocytes was examined. Two linking antibodies were used to bind the dPGL to a rapidly growing test organism, S. aureus, a murine IgM mAb specific for the terminal glycoside of PGL-1, and a rabbit IgG anti-mouse IgM which bound the staphylococcal protein A via its Fc region. Examination by transmission EM of human monocyte-derived macrophages which had ingested staphylococci either coated with both antibodies and dPGL, or coated only with the IgG and IgM antibodies, demonstrated the presence of bacteria in phagosomes of control and IFN-gamma-activated macrophages. Activation of the macrophage monolayers by pretreatment with IFN-gamma markedly increased their staphylocidal activity. When dPGL coated staphylococci were ingested, killing by both control and IFN-gamma-activated macrophages was completely blocked. These results, suggesting that PGL-1 can scavenge reactive oxygen species and prevent microbial death within the phagosome, may in part explain the intracellular survival of M. leprae in certain cell types.
来自麻风分枝杆菌的纯化酚糖脂-1（PGL-1）和脱磷酸酚糖脂（dPGL）可阻止完整吞噬细胞和无细胞抗菌系统对细菌的杀伤作用。这两种糖脂完全消除了乙醛-黄嘌呤氧化酶（XO）-Fe2+系统的抗菌作用。由于该系统的细胞毒性受到过氧化氢酶、超氧化物歧化酶（SOD）、甘露醇和乙醇的抑制，但不受加热后的SOD或过氧化氢酶的抑制，这些数据表明毒性是由哈伯-韦斯反应产生的羟基自由基（OH·）所致。XO系统中的抗菌杀伤作用因添加PGL-1或dPGL而被完全阻断，这表明这些糖脂可作为OH·清除剂。还观察到PGL-1和dPGL对髓过氧化物酶（MPO）-H2O2-卤化物系统的细胞毒性有一定的保护作用。以氯离子而非碘离子作为卤化物时，MPO系统的抗菌活性被消除。研究了麻风分枝杆菌衍生的糖脂对完整吞噬细胞杀伤细菌的影响。使用两种连接抗体将dPGL与快速生长的测试生物体金黄色葡萄球菌结合，一种是对PGL-1末端糖苷具有特异性的鼠IgM单克隆抗体，另一种是通过其Fc区域与葡萄球菌蛋白A结合的兔抗鼠IgM IgG。通过透射电子显微镜检查摄取了同时包被有两种抗体和dPGL的葡萄球菌或仅包被有IgG和IgM抗体的葡萄球菌的人单核细胞衍生巨噬细胞，结果表明在对照巨噬细胞和经γ干扰素激活的巨噬细胞的吞噬体中均存在细菌。用γ干扰素预处理激活巨噬细胞单层可显著增强其杀葡萄球菌活性。当摄取包被有dPGL的葡萄球菌时，对照巨噬细胞和经γ干扰素激活的巨噬细胞的杀伤作用均被完全阻断。这些结果表明PGL-1可清除活性氧并防止吞噬体内的微生物死亡，这可能部分解释了麻风分枝杆菌在某些细胞类型中的细胞内存活现象。
