CANDIDA ADHERENCE & PENETRATION OF VASCULAR ENDOTHELIUM

念珠菌依从性

• 批准号: 3129448
• 负责人: John E Edwards
• 金额: $ 7.98万
• 依托单位: LOS ANGELES COUNTY HARBOR-UCLA MED CTR
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-09-01 至 1988-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3129448
• 关键词: Candida; affinity chromatography; candidiasis; cell adhesion; cell wall; electron microscopy; electrophoresis; host organism interaction; human subject; leukocytes; membrane activity; microorganism immunology; monocyte; neutrophil; pathologic process; phagocytosis; radiotracer; vascular endothelium

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.

在过去的二十年里，有相当大的增长 播散性念珠菌病，特别是在免疫功能低下的患者中， 复杂的术后病人，以及重症监护环境中的新生儿。 这些研究旨在阐明血液生成的过程 散布的念珠菌生物在逃离血管内皮细胞时穿过内皮细胞 血管间隔侵犯实质组织。一项体外试验表明 已被开发用于量化白念珠菌和其他 非白色念珠菌对人、牛和兔血管的作用 内皮细胞。已发现兔抗灭活念珠菌细胞的抗血清 阻断对兔内皮细胞的黏附：该抗血清将 被亲和层析吸收以去除阻隔成分 间接鉴定引起粘附性的念珠菌成分。 念珠菌黏附成分的进一步表征将是 通过去除细胞壁(可能还有细胞膜)部分来完成， 选择性地使特定组件失活，并涂覆载体细胞或 颗粒与去除和处理的部分，以量化粘附性。 我们的封闭抗血清，经过亲和层析，将被 与这些提取的细胞壁部分进行测试以确定 念珠菌介导血管内皮细胞成分的进一步定义 坚持不懈。 念珠菌与血管内皮细胞的黏附发生在循环环境中 细胞和体液成分；与 上皮细胞表面的粘附性。两者之间复杂的相互作用 生物体、内皮细胞和这些血液成分很可能。进一步 在这方面的研究将侧重于四个领域：a)探索 内皮诱导的假丝酵母菌吞噬功能和 通过循环中性粒细胞和单核细胞杀伤，b)开发一种方法 量化念珠菌和/或吞噬细胞引起的内皮损伤，c) 白细胞黏附和迁移的特征， 假丝酵母菌侵袭内皮细胞，d)念珠菌可能的调节作用 最近定义的特定白细胞多肽对内皮细胞的黏附 氨基酸序列。 这些研究的长期目标是阐明 念珠菌在体外对血管内皮细胞的黏附和穿透 可以开发出改变组织侵袭事件的方法 兔血源性念珠菌病模型的建立及最终患者 易受侵袭性血源性念珠菌感染。