INDUCTION OF PROCOAGULANT MOLECULES IN HUMAN MONOCYTES

如果一个人遵循延迟性皮肤过敏的组织学过程，

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.