MONOCYTE ACTIVATION ANTIGENS IN MULTIPLE SCLEROSIS

人外周血单核细胞暴露于细菌产物， 佛波酯、环腺苷酸（cAMP）和cAMP激动剂 刺激膜活化抗原的表面表达， 糖蛋白Mo 3。 Mo 3被两种单克隆抗体Mo 3e识别 (IgM)和Mo 3f（IgG）。Mo 3的表面表达在 未刺激的单核细胞，但在刺激的单核细胞上以高密度表达， 单核细胞和炎性组织中发现的单核细胞。 我们发现 Mo 3在循环单核细胞上的表达增加， 慢性进展型多发性硬化症（CPMS）和复发缓解型MS （RRMS）。 我们还没有发现增加表面钼3（sMo 3）在任何其他 疾病对照组检测。 初步研究表明Mo 3可能是尿激酶纤溶酶原 活化受体和可能具有作用的迁移抑制因子 (MIF)功能 因此，Mo 3+单核细胞可以被引发从单核细胞迁移。 血液进入组织。 MS单核细胞表达增加的sMo 3表明 单核细胞的体内刺激是一个持续的过程。 我们提出 在本申请中，完成目标#1中的临床相关性， 检查MS Mo 3+单核细胞是否表达其他表型和功能 目的#2中激活的相关性;使用 目标#3中的Mo 3 cDNA。

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.