MONOCYTE ACTIVATION ANTIGENS IN MULTIPLE SCLEROSIS

多发性硬化症中的单核细胞激活抗原

基本信息

批准号：
2267874
负责人：
PAULA DORE-DUFFY
金额：
$ 15.34万
依托单位：
WAYNE STATE UNIVERSITY
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 1996-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2267874
关键词：
MHC class II antigen antibody receptor antigen presentation cellular pathology complementary DNA connective tissue disorder cyclic AMP flow cytometry gene expression human subject interleukin 2 leukocyte activation /transformation monocyte multiple sclerosis nervous system disorder northern blottings plasminogen activator prostaglandins receptor surface antigens tissue /cell culture vascular endothelium

MHC class II antigen antibody receptor antigen presentation cellular pathology complementary DNA connective tissue disorder cyclic AMP flow cytometry gene expression human subject interleukin 2 leukocyte activation /transformation monocyte multiple sclerosis nervous system disorder northern blottings plasminogen activator prostaglandins receptor surface antigens tissue /cell culture vascular endothelium

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项目摘要

Exposure of human peripheral blood monocytes to bacterial products, phorbol esters, cyclic adenosine monophosphate (cAMP) and cAMP agonists stimulate the surface expression of a membrane activation antigen, the glycoprotein Mo3. Mo3 is recognized by two monoclonal antibodies Mo3e (IgM) and Mo3f (IgG). Surface expression of Mo3 is barely detectable on nonstimulated monocytes, but is expressed in high density on stimulated monocytes and monocytes found in inflammatory tissue. We have found increased expression of Mo3 on circulating monocytes from patients with chronic progressive multiple sclerosis (CPMS) and relapsing remitting MS (RRMS). We have not found increased surface Mo3 (sMo3) in any other disease control group tested. Preliminary studies indicate that Mo3 may be the urokinase plasminogen activator receptor and may have a role in migration inhibition factor (MIF) function. Thus, Mo3+ monocytes may be primed for migration from the blood into the tissue. That MS monocytes express increased sMo3 suggests that in vivo stimulation of monocytes is an ongoing process. We propose in this application to complete clinical correlations in aim #1; to examine whether MS Mo3+ monocytes express other phenotypic and functional correlates of activation in aim #2; to examine Mo3 gene expression using Mo3 cDNA in aim #3.

将人外周血单核细胞暴露于细菌产物中，凤凰酯，环状腺苷单磷酸（CAMP）和营地激动剂刺激膜激活抗原的表面表达，糖蛋白MO3。 MO3通过两种单克隆抗体MO3E识别（IgM）和MO3F（IgG）。 MO3的表面表达几乎无法在未刺激的单核细胞，但在刺激上以高密度表示在炎症组织中发现的单核细胞和单核细胞。我们找到了来自患者的循环单核细胞对MO3的表达增加慢性进行性多发性硬化症（CPM）和复发汇出MS （RRMS）。我们尚未发现其他任何其他人的表面MO3（SMO3）增加测试疾病对照组。初步研究表明MO3可能是尿激酶纤溶酶原激活剂受体，可能在迁移抑制因子中起作用（MIF）函数。因此，MO3+单核细胞可能被启发用于迁移将血液输入组织。 MS单核细胞表达增加SMO3建议单核细胞的体内刺激是一个持续的过程。我们建议在此应用程序中，在AIM＃1中完成临床相关性；到检查MS MO3+单核细胞是否表达其他表型和功能 AIM＃2中的激活相关；使用MO3基因表达使用 AIM＃3中的MO3 cDNA。