Thrombolytic properties of leukocytes from peripheral blood in healthy subjects and in patients with acute cerebral ischemia

Polymorphonuclear leukocytes are activated in acute ischemic stroke. Activa ted polymorphonuclear leukocytes may contribute to thrombolysis by proteoly tic degradation of fibrin and by modification of the plasminogen system. We used an in vitro thrombolysis model to investigate (1) thrombolytic proper ties of leukocytes in young and healthy subjects, (2) to test the hypothesi s of increased polymorphonuclear leukocyte-associated thrombolysis in patie nts with acute cerebral ischemia, and (3) to assess plasminogen-dependent a nd -independent thrombolytic properties of polymorphonuclear leukocyte elas tase. Coincubation of polymorphonuclear leukocytes with fibrin clots led to increased thrombolysis, a process reaching statistical significance after a hours [1x10(7) polymorphonuclear leukocytes/mL; 12.8+/-1.9% (mean+/-SEM), spontaneous clot lysis: 7.3+/-0.7%]. Polymorphonuclear leukocytes inside c lots caused more efficient thrombolysis than polymorphonuclear leukocytes i n the incubation medium. Spontaneous and polymorphonuclear leukocyte-associ ated lysis tended to be lower in patients with acute cerebral ischemia (n=9 , 24 hours, 9.5+/-1.8% and 12.9+/-2.2%) than in age- and sex-matched contro l subjects (n=8; 12.2+/-2.0% and 17.4+/-1.9%). In the presence of alpha(2)- antiplasmin, thrombolysis tended to be faster with elastase-digested plasmi nogen (miniplasminogen) than with native plasminogen. Purified polymorphonu clear leukocyte elastase itself had no thrombolytic effect. We conclude tha t the thrombolytic capacity of polymorphonuclear leukocytes from peripheral blood is small and slow and may have been overestimated in previous report s. Polymorphonuclear leukocyte thrombolytic activity may not be increased i n acute cerebral ischemia. Miniplasminogen may be an interesting adjunct to plasminogen activators in acute stroke models. (C) 2000 Elsevier Science L td. All rights reserved.