Mechanisms and target sites of damage in killing of Candida albicans hyphae by human polymorphonuclear neutrophils
Mechanisms and target sites of damage in killing of Candida albicans hyphae by human polymorphonuclear neutrophils
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DOI：
10.1086/514156
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发表时间：
1997-12-01
影响因子：
6.4
通讯作者：
Diamond, RD
中科院分区：
文献类型：
--
作者：
Christin, L;Wysong, DR;Diamond, RD
研究了真菌细胞损伤的靶点，以确定中性粒细胞介导的白色念珠菌菌丝的杀灭机制，中性粒细胞诱导的菌丝细胞壁损伤，其证据是细胞壁糖蛋白的释放和共聚焦显微镜下的变化。损伤发生在中性粒细胞颗粒提取物存在的情况下，不需要氧化剂。然而，菌丝表面糖蛋白的氧化与杀菌活性的平行增加密切相关，这表明氧化剂确实对细胞壁造成了最大的破坏，中性粒细胞氧化剂也诱导了菌丝DNA的断裂，主要是单链断裂，表现为核酸酶-S1DNA在单链断裂部位的DNA消化后凝胶迁移增加。菌丝细胞壁和DNA的损伤发生在可检测到的中性粒细胞介导的杀菌作用之前。同样，菌丝氨基酸和核苷酸周转率以及ATP最初上升，然后随着致死效应变得可检测到而下降，因此，在可检测到的真菌细胞死亡之前，中性粒细胞氧化和氧非依赖性机制损害了确定的靶标。
Target sites of fungal cell damage were studied to define mechanisms of neutrophil-mediated killing of Candida albicans hyphae, Neutrophils induced hyphal cell wall damage, as evidenced by release of cell wall glycoproteins and confocal microscopic changes. Damage occurred in the presence of neutrophil granule extracts and did not require oxidants. However, oxidation of hyphal surface glycoproteins correlated strongly with parallel increments in fungicidal activity, suggesting that oxidants did contribute to maximal cell wall damage, Neutrophil oxidants also induced hyphal DNA fragmentation, primarily single-strand breakage, as shown by increased electrophoretic migration after nuclease-S1 DNA digestion at single-strand break sites. The onset of damage to hyphal cell walls and DNA preceded detectable neutrophil-mediated fungicidal effects. Likewise, hyphal amino acid and nucleotide turnover as well as ATP initially rose, then declined as lethal effects became detectable, Thus, preceding detectable fungal cell death, neutrophil oxidative and oxygen-independent mechanisms damaged defined targets.