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TRANSENDOTHELIAL MIGRATION MONONUCLEAR LEUKOCYTES HIV1

跨内皮迁移单核白细胞 HIV1

基本信息

批准号：
6126256
负责人：
HOLLY H BIRDSALL
金额：
$ 23.39万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
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

项目摘要

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、心肌和肌肉发育的过程中， HIV-1感染。这些综合征的临床表现，包括艾滋病-痴呆综合症，已被归因于促炎分子以及白细胞释放的病毒编码蛋白，组织中尽管有新的抗逆转录病毒疗法，治疗血管外表现。长期目标是应用是确定HIV-1感染影响单核白细胞（MNL）穿过血管内皮的迁移屏障和感染细胞在组织外的积累，血管室在上一个供资期间，研究人员和同事发现，HIV-1感染患者的数量白细胞迁移穿过血管内皮细胞是由白细胞的激活状态。这方面的指导假设是， 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; 增加白细胞的随机运动，促进感染巨噬细胞的血管外病灶。可能，某些菌株 HIV-1可以刺激它们感染的白细胞的迁移。可选择地，这些HIV-1毒株优先感染那些白细胞，已经被赋予了穿越血管屏障的能力。三提出了具体的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，促进这些细胞迁移的影响;（2）确定是否迁移性T细胞可以将HIV-1传播给共同迁移的单核细胞，感染可以通过来自邻近内皮细胞的信号传导来调节，细胞外基质蛋白和共迁移的MNL;以及（3）鉴定观察到的HIV-1对跨内皮细胞的作用的分子基础 T细胞和单核细胞的迁移。

项目成果

期刊论文数量（19）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Ligand-stimulated beta 2-adrenergic receptor internalization via the constitutive endocytic pathway into rab5-containing endosomes.

配体刺激的 β2-肾上腺素能受体通过组成型内吞途径内化到含有 rab5 的内体中。

DOI：
10.1242/jcs.108.9.2983
发表时间：
1995
期刊：
Journal of cell science
影响因子：
4
作者：
Moore,RH;Sadovnikoff,N;Hoffenberg,S;Liu,S;Woodford,P;Angelides,K;Trial,JA;Carsrud,ND;Dickey,BF;Knoll,BJ
通讯作者：
Knoll,BJ

Both an altered DNA structure and cellular proteins are involved in protecting a triplex forming an oligopurine-rich sequence from Dam methylation in E. coli.

改变的 DNA 结构和细胞蛋白都参与保护形成富含寡嘌呤序列的三链体免受大肠杆菌中 Dam 甲基化的影响。