ROLE OF MONONUCLEAR LEUKOCYTES IN GRAFT ARTERIOSCLEROSIS

单核白细胞在移植动脉硬化中的作用

• 批准号: 6373611
• 负责人: ANTHONY ROSENZWEIG
• 金额: $ 23.5万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6373611
• 关键词: Adenoviridae; aorta; arteriosclerosis; biological signal transduction; blood vessel transplantation; cell adhesion; cell adhesion molecules; gene expression; helper T lymphocyte; homologous transplantation; human tissue; immunocytochemistry; laboratory rat; leukocyte adhesion molecules; leukocytes; monocyte; monocyte chemoattractant protein 1; polymerase chain reaction; selectins; transfection /expression vector; transplantation immunology; vascular endothelium

DESCRIPTION: (Adapted from the applicant's abstract) The investigator proposes to test the hypothesis that vascular expression of adhesion molecules and MCP-1 are key determinants of mononuclear cell recruitment to transplanted allografts. Further, he hypothesizes that recruited monocytes and T cells contribute to the development of neointimal thickening. To test these hypotheses the applicant proposes to use adenoviral vectors to over express adhesion molecules (ICAM-1, VCAM-1, E-selectin) with MCP-1 or an MCP-1 antagonist in in vitro and in vivo models. In aim 1, they propose to develop the necessary vectors and define in vitro the role of these molecules in MCP-1 in mediating adhesion of specific leukocytes subsets to vascular endothelium under flow conditions. In aim 2, they propose to optimize and characterize in vivo gene transfer in a rat aortic transplant model and in aim 3, they propose to express in transplanted aorta in vivo the molecules that effectively and specifically supported adhesion on mononuclear leukocytes. Finally, they will determine if expression of these molecules leads to recruitment of mononuclear leukocytes into the vessel wall and if recruitment of leukocytes induces neointimal formation.

描述：（根据申请人的摘要改编）调查员 提出测试粘附血管表达的假设 分子和MCP-1是单核细胞募集到的关键决定因素 移植的同种异体移植。 此外，他假设招募单核细胞 T细胞有助于新内膜增厚的发展。 测试 这些假设申请人建议使用腺病毒载体过度 用MCP-1或A 体外和体内模型中的MCP-1拮抗剂。 在AIM 1中，他们建议 开发必要的向量并在体外定义这些作用 MCP-1中的分子在介导特定白细胞的粘附于对 血管内皮在流动条件下。 在AIM 2中，他们建议 优化和表征大鼠主动脉移植中体内基因转移 在AIM 3中，他们建议在体内移植主动脉中表达 有效，有效地支持粘附在上面的分子 单核白细胞。 最后，他们将确定这些表达是否表达 分子导致单核白细胞募集到血管中 墙壁，如果白细胞募集会诱导新的形成。

项目成果

Adhesion of monocytes to vascular cell adhesion molecule-1-transduced human endothelial cells: implications for atherogenesis.

单核细胞对血管细胞粘附分子 1 转导的人内皮细胞的粘附：对动脉粥样硬化形成的影响。

• DOI: 10.1161/01.res.82.8.871
• 发表时间: 1998
• 期刊: Circulation research
• 影响因子: 20.1
• 作者: Gerszten,RE;Lim,YC;Ding,HT;Snapp,K;Kansas,G;Dichek,DA;Cabañas,C;Sánchez-Madrid,F;GimbroneJr,MA;Rosenzweig,A;Luscinskas,FW
• 通讯作者: Luscinskas,FW

Phosphorylation of the cytoplasmic domain of E-selectin is regulated during leukocyte-endothelial adhesion.

E-选择素胞质结构域的磷酸化在白细胞-内皮粘附过程中受到调节。

• 发表时间: 1998
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Yoshida,M;Szente,BE;Kiely,JM;Rosenzweig,A;GimbroneJr,MA
• 通讯作者: GimbroneJr,MA

C-C and C-X-C chemokines trigger firm adhesion of monocytes to vascular endothelium under flow conditions.

C-C 和 C-X-C 趋化因子在流动条件下触发单核细胞与血管内皮的牢固粘附。

• DOI: 10.1111/j.1749-6632.2000.tb06324.x
• 发表时间: 2000
• 期刊: Annals of the New York Academy of Sciences
• 影响因子: 5.2
• 作者: Luscinskas,FW;Gerszten,RE;Garcia-Zepeda,EA;Lim,YC;Yoshida,M;Ding,HA;GimbroneJr,MA;Luster,AD;Rosenzweig,A
• 通讯作者: Rosenzweig,A