TRANSENDOTHELIAL MIGRATION MONONUCLEAR LEUKOCYTES HIV1

跨内皮迁移 单核白细胞 HIV1

• 批准号: 2546431
• 负责人: HOLLY H BIRDSALL
• 金额: $ 22.6万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-12-15 至 2000-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2546431
• 关键词: HIV infections; T lymphocyte; biological signal transduction; cell adhesion; cell migration; chemokine; clinical research; extracellular matrix proteins; human immunodeficiency virus 1; human subject; interferon gamma; interleukin 10; interleukin 4; interleukin 6; leukocyte activation /transformation; leukocyte adhesion molecules; macrophage; monocyte; tissue /cell culture; tumor necrosis factor alpha; vascular endothelium

DESCRIPTION (adapted from the Abstract): Distinctive clinical syndrome involving nervous system, myocardium, and muscle develop in the course of HIV-1 infection. Clinical manifestations of these syndromes, including AIDS-dementia complex, have been attributed to pro-inflammatory molecules and virus-encoded proteins released by leukocytes that migrate into affected tissues. Despite new anti-retroviral therapies, little is achieved in treating extravascular manifestations. The long-term goal of this application is to identify mechanisms whereby HIV-1 infection influences the migration of mononuclear leukocytes (MNLs) across vascular endothelial barrier and the accumulation of infected cells in tissues outside of the vascular compartment. During the previous period of funding the Principal Investigator and coworkers found that the number of HIV-1 infected patients' leukocytes migrating across vascular endothelial cells is determined by the activation state of the leukocytes. The guiding hypothesis in this application is that HIV-1 infection generates cytokines and chemokines that facilitate adhesion between T cells, monocytes, and endothelial cells; increase leukocyte random locomotion; and promote the development of extravascular foci of infected macrophages. Possibly, certain strains of HIV-1 may stimulate migration of the leukocytes they infect. Alternatively, these strains of HIV-1 infect preferentially those leukocytes that are already endowed with ability to migrate across vascular barriers. Three specific aims are proposed to test these hypotheses: (1) to characterize patients' MNLs that carry HIV-1 across endothelial barriers and identify influences that promote migration of these cells; (2) to determine whether migratory T cells can transmit HIV-1 to co-migrating monocytes and how infection may be modulated by signaling from adjacent endothelial cells, extracellular matrix proteins, and co-migrating MNLs; and (3) to identify the molecular basis for the observed effects of HIV-1 on transendothelial migration of T cells and monocytes.

描述（改编自摘要）：独特的临床综合征 在此过程中涉及神经系统，心肌和肌肉 HIV-1感染。 这些综合征的临床表现，包括 艾滋病诱导复合物已归因于促炎分子 和病毒编码的蛋白质由白细胞释放到受影响的白细胞 组织。 尽管有新的抗逆转录病毒疗法，但几乎没有实现 治疗血管外表现。 这个长期目标 应用是确定HIV-1感染影响的机制 单核白细胞（MNL）的迁移 障碍和感染细胞在组织外的组织中的积累 血管室。 在上一期为校长提供资金 研究者和同事发现HIV-1感染患者的数量 跨血管内皮细胞迁移的白细胞由 白细胞的激活状态。 其中的指导假设 应用是HIV-1感染会产生细胞因子和趋化因子 促进T细胞，单核细胞和内皮细胞之间的粘附； 增加白细胞随机运动；并促进发展 感染巨噬细胞的血管外灶。 可能，某些菌株 HIV-1可能刺激其感染白细胞的迁移。 或者， 这些HIV-1菌株优先感染那些白细胞 已经具有跨血管屏障的能力。 三 提出了特定目的来检验这些假设：（1）表征 患者的MNL携带HIV-1跨内皮屏障并识别 影响促进这些细胞迁移的影响； （2）确定是否 迁移的T细胞可以将HIV-1传输到共同迁移的单核细胞，以及如何 感染可以通过来自相邻内皮细胞的信号传导来调节， 细胞外基质蛋白和共迁移MNL； （3）确定 观察到的HIV-1对跨内皮作用的分子基础 T细胞和单核细胞的迁移。