Regulation of Tissue Plasminogen Activator Secretion from Human Endothelial Cells
Tissue plasminogen activator is produced by cultured cells from a variety of sources, and its production can be regulated by hormones,1–3 tumor promoters,3–5 serine proteases,6 and mediators of inflammation.7 Among the cells producing t-PA is the endothelial cell. One of the proposed functions of the vascular endothelium is to maintain or reestablish a homeostatic environment through a variety of pathways, including the production and release of t-PA. In vivo, t-PA levels are elevated following exercise, venous occlusion, or infusion of DDAVP.8.9 The appearance of t-PA is rapid and transient with the initial increase occurring at or before 30 min and returning to baseline by 5–6 hrs. This pattern of t-PA increase and decrease in blood suggests that it results from a release of stored t-PA. In contrast, stimulation of t-PA release from cultured human endothelial cells by thrombin or histamine is much slower, requiring 4–6 hrs to begin, and is also prolonged, continuing for 12–16 hr and only then declining to baseline levels 6,10 This sequence of events has also been reported in the stimulation of t-PA antigen secretion from other cells such as rat granulosa cells following administration of leutinizing hormone.2,3 Thus, this type of response may be characteristic of hormone-induced release of t-PA antigen and may be important in various physiologic and pathologic events.
KeywordsTissue Plasminogen Activator Phorbol Ester Human Endothelial Cell Phorbol Myristate Acetate Antigen Secretion
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