Sasada M, Johnston R B
J Exp Med. 1980 Jul 1;152(1):85-98. doi: 10.1084/jem.152.1.85.
The mechanisms by which macrophages kill ingested microorganisms were explored using Candida albicans and Candida parapsilosis. The results indicate that efficient macrophage candidacidal activity depends upon the generation of oxygen metabolites by the phagocytic cell: (a) peritoneal macrophages from mice infected with bacillus Calmette-Guerin (BCG) or injected intraperitoneally with lipopolysaccharide (LPS) released more superoxide anion (0(2)(-)) during phagocytosis of candida and killed candida better than did resident macrophages; (b) cells of the macrophage-like line J774.1, which released negligible amounts of O(2)(-), could ingest the candida normally but not kill them; (c) killing of candida by resident, LPS- elicited, and BCG-activated macrophages was inhibited by agents that scavenge O(2)(-), hydrogen peroxide (H(2)0(2)), hydroxyl radical (x OH), and singlet oxygen; and (d) all three macrophage types killed C. parapsilosis more effectively than C. albicans, and (7. parapsilosis stimulated a more prompt and vigorous burst of macrophage oxygen consumption and 0(2)(-) release than did C. albicans. Macrophages ingested C. parapsilosis slightly more quickly than C. albicans, but phagocytosis of both strains was equivalent by 60 min of incubation. Although C. albicans contained higher concentrations of the oxygen-metabolite scavengers superoxide dismutase and catalase, neither fungal species scavenged 0(2)(-) or H(2)0(2) effectively; and C. albicans was killed more easily than C. parapsilosis by a xanthine oxidase system that generates primarily H(2)O(2) at pH 7, or 0(2)(-) and x OH at pH 10. Thus, the decreased killing of C. albicans appears to result primarily from the capability of this species to elicit less vigorous stimulation of macrophage oxidative metabolism. This capability may have general relevance to the pathogenicity of microorganisms.
利用白色念珠菌和副念珠菌探索巨噬细胞杀灭摄入微生物的机制。结果表明，高效的巨噬细胞杀念珠菌活性取决于吞噬细胞产生氧代谢产物：(a) 感染卡介苗（BCG）或腹腔注射脂多糖（LPS）的小鼠腹腔巨噬细胞在吞噬念珠菌过程中释放更多超氧阴离子（O₂⁻），且比常驻巨噬细胞更有效地杀灭念珠菌；(b) 巨噬细胞样细胞系J774.1释放的O₂⁻量可忽略不计，但能正常摄取念珠菌却无法将其杀灭；(c) 常驻、LPS诱导及BCG激活的巨噬细胞对念珠菌的杀灭作用受到清除O₂⁻、过氧化氢（H₂O₂）、羟自由基（·OH）和单线态氧的试剂抑制；(d) 所有三种巨噬细胞类型对副念珠菌的杀灭效果均比对白色念珠菌更有效，且副念珠菌比白色念珠菌更迅速、有力地刺激巨噬细胞耗氧量和O₂⁻释放。巨噬细胞摄取副念珠菌的速度比白色念珠菌稍快，但孵育60分钟时两种菌株的吞噬作用相当。尽管白色念珠菌含有较高浓度的氧代谢产物清除剂超氧化物歧化酶和过氧化氢酶，但两种真菌均不能有效清除O₂⁻或H₂O₂；在pH 7时主要产生H₂O₂或在pH 10时产生O₂⁻和·OH的黄嘌呤氧化酶系统能更轻易地杀灭白色念珠菌而非副念珠菌。因此，白色念珠菌杀灭率降低似乎主要是由于该菌种引发巨噬细胞氧化代谢刺激的能力较弱。这种能力可能与微生物的致病性普遍相关。
