HIV INDUCED SYNCYTIA--MOTILITY AND CHEMOATTRACTANT

描述（改编自研究者摘要）：本申请 研究HIV中gp 120-CD 4相互作用诱导的合胞体的性质 被感染的细胞 目前的教条认为合胞体只是巨大的 混乱的细胞体，寿命短，他们不发挥作用， 在HIV发病机制中的积极作用。 然而，通过结合免疫荧光， 电子显微镜和计算机辅助分析的合胞体，P.I. 发现感染的Sup T1细胞在体外形成合胞体， 外周血T细胞1）重组它们的细胞骨架并重新排列 它们的细胞核模仿单个细胞的组织; 2）延伸单个 以类似单个细胞的方式的巨大伪足; 3）沿沿着 多种基质以与单细胞相同的速度; 4）侵入和 破坏胶原蛋白和内皮细胞单层， 巨伪足; 5）吞噬并通过卷曲与T细胞融合 6）释放有效的T细胞化学引诱物;和 7)可以活5.5天。 淋巴结的初步研究 来自HIV感染个体的材料已经鉴定出9个合胞体， 似乎表现出至少一些体外描述的性质。 在这 应用程序，P.I.建议继续他的详细研究， 在体外衍生合胞体，以及花费相当大的努力 研究从HIV感染者的淋巴结活检中获得的合胞体， 个体 他认为，这种“两层”的做法是必要的，因为 患者材料可用性限制了对淋巴结的处理 衍生合胞体 体外研究将包括1）详细 观察细胞在融合过程中的行为; 2）测试融合过程中的细胞行为。 融合的每个步骤对肌动蛋白聚合的依赖性; 3）表征 合胞体介导的趋化性; 4）用T 细胞; 5）表征合胞体释放的化学引诱物， 6）测试是否有针对化学引诱物的抗体或 高浓度化学引诱物可阻断合胞体形成; 7） 研究合胞体如何吞噬T细胞; 8）研究合胞体如何破坏 胶原和内皮细胞单层; 9）将体外工作扩展到 巨噬细胞 一旦用体外细胞建立了周长， 来自感染患者淋巴结的合胞体将在 相似的时尚。

DESCRIPTION (Adapted from investigator's abstract): This application examines the nature of syncytia induced by the gp120-CD4 interaction in HIV infected cells. Current dogma would say that syncytia are only giant disorganized cell bodies with short life spans and that they do not play an active role in HIV pathogenesis. However, by combining immunofluorescent, electron microscopic and computer assisted analysis of syncytia, the P.I. has discovered that syncytia formed in vitro by infected Sup T1 cells or peripheral blood T-cells 1) reorganize their cytoskeleton and rearrange their nuclei to mimic the organization of a single cell; 2) extend a single giant pseudopod in a fashion similar to a single cell; 3) crawl along a variety of substrates with the same velocity as single cells; 4) invade and disorganize collagen and endothelial monolayers through the extension of giant pseudopods; 5) phagocytose as well as fuse with T cells by coiling pseudopods around T cells; 6) release a potent T cell chemoattractant; and 7) can live for as long as 5.5 days. Preliminary studies with lymph node material from an HIV-infected individual have identified 9 syncytia which seem to exhibit at least some of the properties described in vitro. In this application, the P.I. proposes to continue his detailed studies with syncytia derived in vitro, as well as spend a considerable amount of effort studying syncytia obtained from lymph node biopsies of HIV-infected individuals. He believes that this "two tiered" approach is necessary since the availability of patient material limits what can be done with lymph-node derived syncytia. The in vitro studies will include 1) Detailed observations of the behavior of cells during fusion; 2) Testing the dependency of each step of fusion on actin polymerization; 3) Characterizing syncytium mediated chemotaxis; 4)Testing known chemoattractants with T cells; 5) Characterizing the chemoattractant released from syncytia and generating antiserum to it; 6) Testing if antibody to the chemoattractant or high concentrations of chemoattractant can block syncytia formation; 7) Studying how syncytia phagocytose T-cell; 8) Studying how syncytia disrupt collagen and endothethial monolayers; 9) Extending the in vitro work to macrophages. Once the perimeters are established with cells in vitro , syncytia derived from lymph nodes of infected patients will be studied in a similar fashion.