ORIGINAL ARTICLESPoly-l-histidine downregulates fibrinolysisChu, Arthur Ja; Mathews, Suresh TbAuthor Information aDepartment of Surgery and bDepartment of Pathology, School of Medicine, Wayne State University, Detroit, Michigan, USA. Correspondence and requests for reprints to Arthur J. Chu, 416 Lande Medical Research Building, 550 East Canfield, Detroit, MI 48201, USA. Tel: +1 313 577 8643; fax: +1 313 745 2964; e-mail: firstname.lastname@example.org Received 21 October 2002 Revised 13 December 2002 Accepted 24 December 2002 Blood Coagulation & Fibrinolysis: October 2003 - Volume 14 - Issue 7 - p 627-632 Buy Abstract The elevated level of histidine-rich glycoprotein was considered a risk factor of inherited thrombophilia. However, the mode of action remains largely unclear. In the current study, we employ poly-l-histidine (PLH) mimicking the histidine-rich region and determine whether PLH modulates urokinase (uPA)-dependent fibrinolysis. In an in vitro model, turbidity appearance and clearance monitored fibrin polymer formation and lysis, respectively. Fibrin polymer formed upon fibrinogen incubation with thrombin. In the presence of uPA or plasmin, fibrin polymer lysis took place in a dose-dependent manner as a function of time. We demonstrated that PLH significantly downregulated uPA-dependent fibrinolysis. PLH had no effect on plasminogen activation, as evidenced by no inhibitions on either uPA amidolytic activity or plasmin formation derived from its zymogen. Nor did PLH show any inhibition on plasmin amidolytic activity. PLH caused a profound delay of plasmin-dependent fibrinolysis upon pre-incubation of either plasmin or fibrinogen with PLH. The observations taken together suggest that the complex [plasmin–PLH–fibrin] formation significantly delayed plasmin-dependent fibrinolysis. © 2003 Lippincott Williams & Wilkins, Inc.