The role of the classical and alternate complement pathways in host defenses against Cryptococcus neoformans infection.
The role of the classical and alternate complement pathways in host defenses against Cryptococcus neoformans infection.
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DOI：
10.4049/jimmunol.112.6.2260
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发表时间：
1974-06
影响因子：
4.4
通讯作者：
R. Diamond;J. May;M. Kane;M. Frank;J. Bennett
中科院分区：
文献类型：
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作者：
R. Diamond;J. May;M. Kane;M. Frank;J. Bennett
补体与已知人类白细胞吞噬新型隐球菌所必需的热不稳定因子之间的关系已被检查。新型隐球菌或纯化的隐球菌多糖消耗了豚鼠血清中 36.2% 至 76.3% 的晚期补体成分 (C3-9)。使用 C2 缺陷型人血清和 C4 缺陷型豚鼠血清进行的吞噬研究可以评估经典 (C142) 补体途径和替代补体途径在这些生物体吞噬作用中的作用。 30 分钟时，仅具有替代途径功能的血清中每个中性粒细胞摄入的隐球菌数量（吞噬指数）是具有完整的经典补体途径和替代补体途径的血清中发现的隐球菌数量的 40% 至 60%。当纯化的 C2 或 C4 添加回相应的缺陷血清中时，吞噬指数增加到使用两个补体途径均活跃的相应正常血清获得的范围。 2小时后，缺陷血清的吞噬指数与正常血清的吞噬指数相等。因此，早期经典补体成分对于最佳吞噬动力学是必需的。补体晚期成分是吞噬作用所必需的这一事实是通过 Ca++ 和 Mg++ 与 EDTA 的螯合抑制反应的事实确定的，56°C 加热和使用通过眼镜蛇毒因子耗尽补体晚期成分的血清也会抑制反应。这些研究中使用的血清均未通过间接荧光抗体技术检测到抗隐球菌抗体，但隐球菌在 0°C 吸收人血清时，吞噬指数降低至正常值的 10% 左右。吸收后活性丧失被证明是由于激活 C142 途径所需的特异性抗体的丧失以及激活替代途径所需的备解素的丧失。经典补体途径似乎主要起激活替代途径的作用，而替代途径又负责调理作用。缺乏备解素或热不稳定备解素因子B的血清在调理活性方面明显缺乏。在前一种情况下，添加备解素可恢复最佳动力学。因此，正常血清中经典途径的功能不能充分介导调理作用。与血清不同，脊髓液不会调理隐球菌。使用荧光抗人β1C，从四名隐球菌性脑膜炎患者的脊髓液中获得的隐球菌表面检测到很少或没有检测到补体，但在这些患者的新鲜血清中孵育后在隐球菌上发现了补体。然而，三分之二的活动性疾病患者的脑脊液可以恢复被隐球菌吸收的新鲜血清的调理活性。
The relationship between complement and the heat labile factors known to be necessary for phagocytosis of Cryptococcus neoformans by human leukocytes has been examined. C. neoformans or purified cryptococcal polysaccharide consumed 36.2 to 76.3% of late complement components (C3-9) in guinea pig serum. Phagocytic studies with C2-deficient human serum and C4-deficient guinea pig serum permitted evaluation of the roles of the classical (C142) and alternate complement pathways in the phagocytosis of these organisms. The number of cryptococci ingested per neutrophil (phagocytic index) at 30 min in sera with only alternate pathway function was 40 to 60% of that found in sera with both classical and alternate complement pathways intact. When purified C2 or C4 was added back to the corresponding deficient sera, phagocytic indices increased to ranges obtained by using corresponding normal sera with both complement pathways active. By 2 hr, phagocytic indices for deficient sera equaled phagocytic indices for normal sera. Early classical complement components were therefore required for optimum phagocytic kinetics. The fact that late components of complement were required for phagocytosis was established by the fact that chelation of Ca++ and Mg++ with EDTA inhibited the reaction, as did heating at 56°C and use of serum depleted of the late components of complement by cobra venom factor. None of the sera used in these studies had detectable anti-cryptococcal antibody by an indirect fluorescent antibody technique, but absorption of human sera at 0°C with cryptococci lowered phagocytic indices to about 10% of normal. The loss of activity after absorption was demonstrated to be due to loss of specific antibody which was required to activate the C142 pathway as well as to loss of properdin which was required to activate the alternate pathway. The classical complement pathway appeared to be functioning primarily to activate the alternate pathway, which in turn was responsible for opsonization. Serum depleted of properdin or of the heat labile properdin factor B was markedly deficient in opsonic activity. In the former case addition of properdin restored optimal kinetics. Thus, function of the classical pathway in normal serum did not adequately mediate opsonization. Unlike serum, spinal fluid did not opsonize cryptococci. With fluorescent anti-human β1C, little or no complement was detectable on the surface of cryptococci obtained from the spinal fluid of four patients with cryptococcal meningitis, but was found on cryptococci after incubation in fresh sera from these patients. However, cerebrospinal fluid from two of three patients with active disease could restore opsonic activity of fresh serum absorbed with cryptococci.