CANDIDA ADHERENCE & PENETRATION OF VASCULAR ENDOTHELIUM

在过去的二十年里， 播散性念珠菌病，特别是免疫功能低下的患者， 复杂的术后患者和重症监护室中的新生儿。 这些研究的目的是阐明造血系统 传播念珠菌微生物穿过内皮，因为它们逃离 血管室侵入实质组织。 体外测定具有 已被开发用于量化C.白色念珠菌和其他 人、牛和兔血管的非白色念珠菌属 内皮细胞 已发现抗杀念珠菌细胞的兔抗血清， 阻断对兔内皮细胞的粘附：这种抗血清将 通过亲和色谱法吸收，以除去用于 间接鉴定导致粘附的念珠菌成分。 念珠菌粘附成分的进一步表征将在 通过除去细胞壁（和可能的细胞膜）部分来完成， 选择性灭活特定组分，并包被载体细胞，或 具有去除和处理的级分的颗粒以量化粘附。 我们的阻断抗血清，经过亲和层析，将被 针对这些提取的细胞壁部分进行测试以证实， 进一步确定念珠菌介导内皮细胞的成分 坚持。 念珠菌粘附于血管内皮发生在循环的环境中， 细胞和体液成分;一个独特的环境， 粘附于上皮表面。 复杂的相互作用， 生物体、内皮细胞和这些血液元素是可能的。 进一步 研究将集中在这方面的四个领域： 可能的内皮诱导的念珠菌吞噬作用的改善， 通过循环的PMN和单核细胞杀伤，B）开发一种方法， 定量念珠菌和/或吞噬细胞诱导的内皮损伤，c） 白细胞粘附和迁移的表征， 念珠菌侵入内皮，d）念珠菌的可能调节 内皮细胞粘附的特异性白细胞肽最近被定义在 氨基酸序列 这些研究的长期目标是阐明 念珠菌粘附和穿透血管内皮，在体外，所以 可以开发方法来改变组织侵入的事件， 家兔血源性念珠菌病模型，并最终在患者 易受侵袭性血源性念珠菌感染。

During the past two decades, there has been a considerable increase in disseminated candidiasis, particularly in immunocompromised patients, complicated postoperative patients, and neonates in intensive care settings. These studies are designed to elucidate the process by which hematogenously spread Candida organisms traverse the endothelium as they escape from the vascular compartment to invade parenchymal tissues. An in vitro assay has been developed to quantify the adherence of C. albicans and other non-albicans Candida species to human, bovine, and rabbit vascular endothelium. Rabbit antiserum to killed Candida cells has been found to block adherence to rabbit endothelial cells: this antiserum will be absorbed by affinity chromatography to remove the blocking components for indirect identification of Candida constituents responsible for adherence. Further characterization of Candida adherence constituents will be accomplished by removing cell wall (and possibly cell membrane) fractions, selectively inactivating specific components, and coating carrier cells or particles with the removed and treated fractions to quantify adherence. Our blocking antiserum, subjected to affinity chromatography, will be tested against these extracted cell wall fractions for substantiation and further definition of components of Candida which mediate endothelial adherence. Candida adherence to vascular endothelium occurs in a milieu of circulating cellular and humoral components; a unique environment when compared to adherence on epithelial surfaces. Complex interactions between the organism, endothelial cells, and these blood elements are likely. Further studies will focus on four areas within this context: a) exploration of possible endothelial induced improvement in Candida phagocytosis and killing by circulating PMNs and monocytes, b) development of a method to quantify Candida and/or phagocytic cell induced endothelial damage, c) characterization of leukocyte adherence to, and migration through, endothelium invaded by Candida, d) possible modulation of Candida endothelial adherence by specific leukocytic peptides recently defined in amino acid sequence. The long range goal of these studies is to elucidate the mechanisms of Candida adherence and penetration of vascular endothelium, in vitro, so that methods can be developed to modify the events of tissue invasion in the rabbit model of hematogenous candidiasis and ultimately in patients susceptible to invasive hematogenous Candida infections.