MONOCYTE-MEDIATED SERUM-INDEPENDENT DAMAGE TO HYPHAL AND PSEUDOHYPHAL FORMS OF CANDIDA-ALBICANS INVITRO
MONOCYTE-MEDIATED SERUM-INDEPENDENT DAMAGE TO HYPHAL AND PSEUDOHYPHAL FORMS OF CANDIDA-ALBICANS INVITRO
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DOI：
10.1172/jci110010
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发表时间：
1981-01-01
影响因子：
15.9
通讯作者：
HAUDENSCHILD, CC
中科院分区：
文献类型：
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作者：
DIAMOND, RD;HAUDENSCHILD, CC
人外周血单核细胞粘附于C.白念珠菌菌丝在无血清的情况下，破坏菌丝而不完全吞噬它们。加入血清并不能增加附着和损伤。通过先前开发的代谢测定法定量测定菌丝对白细胞诱导的[14 C]胞嘧啶摄取减少。使用遗传性白细胞功能障碍、慢性肉芽肿病和髓过氧化物酶缺乏症患者的细胞表明，髓过氧化物酶非依赖性和非氧化机制有时会损害氧化机制受损的菌丝。正常单核细胞的菌丝损伤被抑制浓度的NaN 3和NaCN，主要影响髓过氧化物酶的活性，以及无卤化物的条件下，过氧化氢酶和推定的拮抗剂次氯酸或单线态O。菌丝碘化，髓过氧化物酶和过氧化氢依赖的单核细胞的过程中，同样受到抑制NaN 3，NaCN和过氧化氢酶。在厌氧条件下，菌丝损伤减少64.0- 68.4%。潜在的非氧化性抗真菌机制抑制剂，铁盐饱和铁螯合剂，和聚阴离子氨基酸聚合物，以中和阳离子蛋白质没有阻止单核细胞的菌丝损伤。从分级分离的正常单核细胞中提取的富含溶酶体颗粒的制剂也不损害菌丝。显然，氧化机制是最重要的损害菌丝由正常单核细胞EM证实，念珠菌菌丝被损坏，并可能被单核细胞杀死，但单核细胞似乎在这个过程中维持显着的损害。在没有血清的情况下，单核细胞的细胞膜变得非常接近念珠菌细胞壁。显然，有些念珠菌可以逃脱这种部分吞噬，因为它们可以自由漂浮，囊泡状三层膜残留覆盖菌丝表面。单核细胞似乎被破坏的相互作用与念珠菌菌丝比中性粒细胞。
Human peripheral blood monocytes attached to C. albicans hyphae in the absence of serum and damaged the hyphae without completely ingesting them. Attachment and damage was not augmented by serum addition. Damage to hyphae was quantitated by a previously developed metabolic assay that measured leukocyte-induced reduction in [14C]cytosine uptake by the hyphae. Use of cells from patients with hereditary leukocyte function disorders, chronic granulomatous disease, and myeloperoxidase deficiency indicated that myeloperoxidase-independent and nonoxidative mechanisms could sometimes damage hyphae where oxidative mechanisms were impaired. Hyphae damage by normal monocytes was inhibited by concentrations of NaN3 and NaCN that primarily affect myeloperoxidase activity, as well as by halide-free conditions, catalase and putative antagonists of hypochlorous acid or singlet O. Hyphae iodination, a myeloperoxidase and hydrogen peroxide-dependent process of monocytes, was similarly inhibited by NaN3, NaCN and catalase. Under anaerobic conditions, hyphae damage was reduced by 64.0-68.4%. Potential nonoxidative antifungal mechanism inhibitors, Fe salts to saturate Fe chelators, and polyanionic amino acid polymers to neutralize cationic proteins did not block hyphae damage by monocytes. Preparations rich in lysosomal granules from fractionated normal monocytes also did not damage hyphae. Apparently oxidative mechanisms were most important for damage to hyphae by normal monocytes EM confirmed that Candida hyphae were damaged and probably killed by monocytes, but monocytes appeared to sustain significant damage in the process. In the absence of serum, monocyte cell membranes became closely approximated to Candida cell walls. Apparently some Candida could escape this partial engulfment, as they were seen floating free with vesicular trilaminar membrane remnants covering hyphal surfaces. Monocytes appeared to be damaged by interactions with Candida hyphae more than neutrophils.