Summary
The objective of this study was to characterize the plasmin-induced stimulation of
leukotriene (LT) B4 biosynthesis in human peripheral monocytes (PM). Plasmin up to
175 × 10-3 CTA U/ml triggers a concentration-dependent release of 5-lipoxygenase-derived LTB4
while release of the cyclooxygenase products thromboxane (TX) B2 and prostaglandin (PG) E2 remained unaffected. The stimulatory effect appeared to be specific in as much as
1) it was found in PM, but not in polymorphonuclear neutrophils (PMN), 2) it requires
the lysine binding sites of plasmin molecule since it was inhibited by the lysine
analogues 6-aminohexanoic acid (6-AHA) and trans-4(aminometh-yl)cyclohexane-l-carboxylic
acid (t-AMCA), 3) the intact catalytic center of plasmin is required since neither
plasminogen nor catalytic center-blocked plasmin share the stimulatory effect of active
plasmin, 4) other serine proteases such as a-chymotrypsin, human neutrophil elastase
and cathepsin G did not stimulate release of detectable amounts of LTB4 from PM. In
addition, catalytic center-blocked plasmin antagonized the stimulatory effect of active
plasmin. Plasmin-mediated monocyte activation apparently proceeds via a pertussis
toxin-sensitive G protein. Plasmin did not increase inositol (1,4,5) trisphosphate
levels, but a time- and concentration-dependent stimulation of cyclic GMP formation
was observed. The data show that plasmin is a specific stimulus for human peripheral
monocytes. Plasmin may be an important link between the coagulation cascade and inflammatory
reactions.