PURIFICATION AND CHARACTERIZATION OF FACTORS PRODUCED BY ASPERGILLUS-FUMIGATUS WHICH AFFECT HUMAN CILIATED RESPIRATORY EPITHELIUM
PURIFICATION AND CHARACTERIZATION OF FACTORS PRODUCED BY ASPERGILLUS-FUMIGATUS WHICH AFFECT HUMAN CILIATED RESPIRATORY EPITHELIUM
复制标题
DOI：
10.1128/iai.63.9.3266-3271.1995
复制
发表时间：
1995-09-01
影响因子：
3.1
通讯作者：
WILSON, R
中科院分区：
文献类型：
--
作者：
AMITANI, R;TAYLOR, G;WILSON, R
烟曲霉在呼吸道粘膜上定植的机制尚不清楚，9株烟曲霉临床分离株中有8株在体外培养时表现出纤毛搏动频率增高和呼吸道上皮损伤。这些变化似乎同时发生，两株白念珠菌临床分离株的培养物对纤毛上皮无影响。我们从临床分离的A.烟熏。cilioinhibitory活性是热不稳定的，减少透析，并部分提取到氯仿中，该活动与高和低分子量的因素，通过凝胶过滤Sephadex G-50上确定。通过反相高效液相色谱法进一步纯化了一种低分子量的纤毛抑制因子，并通过质谱法证实其为A.烟熏。在浓度高于0.2 μ g/ml时，胶霉毒素显著减慢与上皮损伤相关的纤毛搏动频率;其他曲霉毒素，即，烟曲霉素和helvolic酸也是纤毛抑制的，但浓度高得多。高分子量（大于或等于35，000和25，000）的纤毛抑制物质既没有弹性蛋白分解活性也没有蛋白水解活性，仍有待鉴定。烟曲霉产生许多生物活性物质，其减慢纤毛跳动并损伤上皮，并且其可影响气道的定殖。
The mechanisms by which Aspergillus fumigatus colonizes the respiratory mucosa are unknown, Culture filtrates of eight of nine clinical isolates of A, fumigatus stowed ciliary beat frequency and damaged human respiratory epithelium in vitro. These changes appeared to occur concurrently, Culture filtrates of two clinical isolates of Candida albicans had no effect on ciliated epithelium. We have purified and characterized cilioinhibitory factors of a clinical isolate of A. fumigatus. The cilioinhibitory activity was heat labile, reduced by dialysis, and partially extractable into chloroform, The activity was associated with both high- and low-molecular-weight factors, as determined by gel filtration on Sephadex G-50. A low-molecular-weight cilioinhibitory factor was further purified by reverse-phase high-performance liquid chromatography and shown by mass spectrometry to be gliotoxin, a known metabolite of A. fumigatus. Gliotoxin significantly slowed ciliary beat frequency in association with epithelial damage at concentrations above 0.2 mu g/ml; other Aspergillus toxins, i.e., fumagillin and helvolic acid, were also cilioinhibitory but at much higher concentrations. High-molecular-weight (greater than or equal to 35,000 and 25,000) cilioinhibitory materials had neither elastolytic nor proteolytic activity and remain to be identified, Thus, A. fumigatus produces a number of biologically active substances which slow ciliary beating and damage epithelium and which may influence colonization of the airways.