INDUCTION OF PROCOAGULANT MOLECULES IN HUMAN MONOCYTES

如果遵循迟发性皮肤过敏的组织学过程， 很明显，纤维蛋白的形成是突出的早期， 炎症过程。 然而，随着时间的推移， 损伤。 这一信息意味着一种监管机制， 凝血在这种病变的活动期占主导地位， 平衡在修复阶段向纤维蛋白溶解倾斜。 的 单核细胞/巨噬细胞产生效应分子，这些效应分子对每个细胞都有活性。 凝血-纤维蛋白溶解过程的一面。 更好地描述了 这些活性是激活循环的纤溶酶原激活剂（PA 纤溶酶原转化为纤溶酶，纤溶酶是血浆的主要纤溶酶。 更 最近已经认识到，单核细胞也可以精心制作一种 促凝血活性（PC）。 有证据表明， PC是一个高度特异性的事件，用于诱导PC产生的刺激具有 是多克隆细胞活化剂。 此外，PA和PC上的数据 这意味着当单核细胞较少时，PC可能产生更多量 分化，PA生产随着细胞成熟而增加。 我 建议使用T细胞克隆来定义PC的抗原诱导， 外周血单个核细胞已经对特定的 抗原的 我会将其与淋巴细胞增殖联系起来， 反应的特异性。 单核细胞将被确认为 PC的细胞来源，伴有淋巴细胞影响和代谢 要求正在确定。 本研究的另一个目的是 建立淋巴细胞在PA单核细胞加工中的作用， 确定单核细胞产生PC之间的关系，如果有的话， 和PA。

If one follows the histologic course of delayed cutaneous hypersensitivity, it becomes evident that fibrin formation is prominent early in the inflammatory process. With time, however, the fibrin is cleared from the lesion. This information implies a regulatory mechanism allowing coagulation to predominate in the active phase of such lesions, with the balance tipping toward fibrinolysis in the reparative phase. The monocyte/macrophage produces effector molecules which are active on each side of the clotting-fibrinolysis process. The more well characterized of these activities is plasminogen activator (PA) which activates circulating plasminogen to plasmin, the major fibrinolytic enzyme of plasma. More recently it has been recognized that monocytes also elaborate a procoagulant activity (PC). Whereas there is evidence that production of PC is a highly specific event, stimuli used to induce PC production have been polyclonal cell activators. In addition, the data on both PA and PC imply that PC may be produced in greater quantities when monocytes are less differentiated, with PA production increasing with cell maturity. I propose to use T cell clones to define antigen induction of PC by peripheral blood mononuclear cells that have been sensitized to a specific antigen. I will correlate this to lymphocyte proliferation to confirm the specificity of the response. The monocyte will be confirmed as the cellular source of PC, with lymphocyte influences and metabolic requirements being identified. Another aim of this study will be to establish the role of lymphocytes in monocyte elaboration of PA, and to determine what relation, if any, there is between monocyte production of PC and PA.