FIBRINOLYTIC ACTIVITY (FA) OF NORMAL HUMAN PERIPHERAL BLOOD MONOCYTES (MC)

FA of blood encompasses a large cellular phase in addition to a fluid (plasma) phase. Polymorphonuclear neutrophils (PMN) have been implicated in this cellular activity, and MC have demonstrated fibrinolytic potential. Using a solid phase radiofibrin assay, we have examined FA of normal blood and plasma, and of purified PMN and MC alone, and with purified plasminogen (PLG), mini-plasminogen (mPLG) produced by gMN elastase digestion, or autologous plasma. PMN alone (0.5 x 10⁶/mL) had striking activity (292 ± 25 SEM ng fibrin lysed/h), (n=10 normal subjects) while MC alone (0.5 x 10⁶/ml) had mean FA of 32 ± 4 ng/h, all of which could be accounted for by contaminating PMN in the MC preparations (36 ± 8 ng/h). In comparison, mean whole blood FA wgs 72 ± 4 ng/h, and plasma FA was 22 ± 4 ng/h. When MC (0.5 x 10⁶/ml) were assayed with PLG (2-40 yg/ml) or autologous plasma for 1 h, no significant FA was generated, indicating that neither intrinsic nor PLG-dependent (plasminogen activator, PA) activity of MC contribute significantly to the FA of whole blood as measured by routine 1 h assay, where 70% of measured FA involves the cellular phase. However, with longer assay times (2-6 h), there was time-dependent appearance of FA when MC were mixed with PLG or with autologous plasma. This FA was dependent upon interaction between MC and PLG, since no FA was generated by supernatants of MC preincubated alone, while FA was readily detected in the medium when MC and PLG were mixed. Comparing effects of PLG and mPLG, FA of MC (0.5 x 10⁶/ml) with PLG (40 Ug/ml) was 447 ± 9 ng/3 h, while FA with mPLG (40 pg/ml, an approximate 3-fold molar excess) was 156 ± 5 ng/3 h, indicating a possible role for the N-terminal portion of the PLG molecule (containing kringle domains 1-4 absent in mPLG) in interaction ofg MC and PLG, or of MC-derived PA and PLG. FA of MC (0.5 x 10⁶/ml) in autologous plasma (83±3 ng/3 h) was markedly reduced after lysine-Sepharose PLG depletion (14 ± 1 ng/3 h), and by addition of tranexamic acid (10 mmol/L) (5±1 ng/3 h). Thus, normal peripheral blood monocytes, like PMN, may contribute, albeit in a minor manner, to normal blood fibrinolytic activity, via PLG activation rather than direct proteolysis, and constitute an additional mechanism for interaction between cellular and fluid (plasma) phases in blood fibrinolytic activity.