LYMPHOCYTE ADHERENCE IN MULTIPLE SCLEROSIS

多发性硬化（MS）是中枢神经系统的慢性脱髓鞘疾病， 神经系统 很可能是免疫机制紊乱和/或 炎症反应的调节缺陷是 病理过程导致MS的组织损伤。 前列腺素（PGs）和花生四烯酸的其他产物（C20：4） 代谢是细胞功能的重要调节剂， 炎症 虽然证据是模棱两可的，PG调节免疫 MS患者的功能可能会改变。 我们已经证明， MS患者的淋巴细胞粘附（病毒感染的细胞和髓磷脂）可能 由于单核细胞依赖性和前列腺素E介导的机制， MS单核细胞自发地在组织中产生增加的PGE水平， 文化 因此，增加的淋巴细胞粘附可以在体外实验中进行。 测量单核细胞控制的PGE对T细胞应答的调节 （遵守）。 可能PG介导的调节或控制 淋巴细胞表面受体可以部分解释大部分的 在MS中观察到的免疫表观现象。我们将继续描述 控制淋巴细胞粘附髓鞘的机制，并将评估 外周血单核细胞、单核细胞功能与花生四烯酸 特别是，这些研究将包括评估MS的代谢。 MS单核细胞、CSF白细胞及其代谢产物中的花生四烯酸代谢 与淋巴细胞粘附于髓磷脂的关系。 结果将相互关联 临床特征。 此外，作为我们研究的延伸，我们将 检查单核细胞功能、Ia抗原表达和单核细胞的作用 淋巴细胞粘附。 这些研究很可能会提供 关于单核细胞-前列腺素相互作用及其 在多发性硬化症白细胞功能改变中的作用。

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system. It is likely that disordered immune mechanisms and/or defective regulation of inflammatory responses are central to the pathological processess which result in tissue injury in MS. Prostaglandins (PGs) and other products of arachidonic acid (C20:4) metabolism are important regulators of cell function and local mediators of inflammation. While the evidence is equivocal, PG regulation of immune function may be altered in MS patients. We have shown that increased lymphocyte adherence (virus infected cells and myelin) in MS patients may be due to a monocyte dependent, and prostaglandin E mediated mechanism and that MS monocytes spontaneously produce increased levels of PGE in tissue culture. Thus, increased lymphocyte adherence may be in an in vitro measurement of a monocyte controled PGE modulation of a T-cell response (adherence). It is possible that PG-mediated modulation or control of lymphocyte cell surface receptors can, in part, account for much of the immunologic epiphenomena observed in MS. We will continue to delineate mechanisms which govern lymphocyte adherence to myelin and will evaluate peripheral blood monocytes, monocyte function and arachidonic acid metabolism in MS. In particular, these studies will include evaluation of arachidonic acid metabolism in MS monocytes, CSF leukocytes and their relation to lymphocyte adherence to myelin. Results will be correlated with clinical features. Further, as an extension of our studies, we will examine monocyte function, Ia antigen expression and the role of monocytes in lymphocyte adhesion. It is likely that these studies will provide useful new information on monocyte-prostaglandin interactions and their role in altered leukocyte function in multiple sclerosis.