MONOCYTE ACTIVATION ANTIGENS IN MULTIPLE SCLEROSIS

人类外周血单核细胞接触细菌产品， 佛波酯、环磷酸腺苷(CAMP)和cAMP激动剂 刺激膜激活抗原的表面表达， 糖蛋白MO3。Mo3可被两株单抗Mo3e识别 (IgM)和Mo3f(免疫球蛋白)。表面上几乎检测不到Mo3的表达。 未刺激的单核细胞，但刺激后高密度表达 单核细胞和炎症组织中的单核细胞。我们发现了 慢性支气管炎患者外周血单核细胞表面mO_3表达增加 慢性进行性多发性硬化症与复发缓解型多发性硬化症 (RRMS)。我们没有在任何其他材料中发现表面Mo3(SMo3)增加 疾病对照组进行测试。 初步研究表明，mo3可能是尿激酶型纤溶酶原。 激活剂受体并可能在迁移抑制因子中发挥作用 (MIF)函数。因此，mO_3~+单核细胞可能已准备好从 血液进入组织。MS单核细胞表达增加的sMo3提示 单核细胞的体内刺激是一个持续的过程。我们建议 在此应用程序中完成目标#1中的临床相关性 检查MS m03+单核细胞是否表达其他表型和功能 目的#2；检测mO3基因表达的相关性 Aim#3中的MO3基因。

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.