TRANSENDOTHELIAL MIGRATION MONONUCLEAR LEUKOCYTES HIV1

跨内皮迁移 单核白细胞 HIV1

• 批准号: 2839364
• 负责人: HOLLY H BIRDSALL
• 金额: $ 22.99万
• 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: 1993-12-01 至 2000-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2839364
• 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 涉及神经系统、心肌、肌肉的发育过程 HIV-1 感染。 这些综合征的临床表现包括 艾滋病-痴呆症复合体，归因于促炎分子 和白细胞释放的病毒编码蛋白迁移到受影响的 组织。 尽管有新的抗逆转录病毒疗法，但收效甚微 治疗血管外表现。 本次活动的长远目标 应用程序是确定 HIV-1 感染影响的机制 单核白细胞 (MNL) 跨血管内皮细胞的迁移 屏障和受感染细胞在组织外的积累 vascular compartment. 在上一个资助校长期间 研究人员和同事发现 HIV-1 感染患者的数量 白细胞跨血管内皮细胞的迁移由以下因素决定 白细胞的激活状态。 本研究的指导性假设 应用是HIV-1感染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 受感染巨噬细胞的血管外病灶。 可能某些菌株 HIV-1 可能会刺激其感染的白细胞迁移。 或者， 这些 HIV-1 病毒株优先感染那些 already endowed with ability to migrate across vascular barriers. 三 提出了具体目标来检验这些假设：(1) 表征 患者的 MNL 携带 HIV-1 穿过内皮屏障并识别 促进这些细胞迁移的影响； (2) to determine whether 迁移性 T 细胞可以将 HIV-1 传播给共同迁移的单核细胞，以及如何进行 感染可以通过邻近内皮细胞的信号调节， 细胞外基质蛋白和共迁移 MNL； and (3) to identify 观察到的 HIV-1 对跨内皮细胞影响的分子基础 T 细胞和单核细胞的迁移。