SummaryApolipoprotein(a), the plasminogen-like component of lipoprotein(a), is transformed into fragments by polymorphonuclear neutrophils (PMNs) elastase. Since stimulated PMNs express urokinase-type plasminogen activator (uPA), we sought to investigate the relevance of apo(a) fragmentation on plasminogen activation by neutrophils. Freshly isolated human PMNs stimulated by a 10 kringle recombinant apo(a), r-apo(a), activate plasminogen in a specific and saturable manner (Km = 476 ± 42 nM, Vmax = 896 ± 18 pmol min-1). This activation is prevented by amiloride, an inhibitor of u-PA, and ɛ-aminocaproic acid, ɛ-ACA, a lysine analogue that blocks plasminogen binding to PMNs. Stimulation of PMNs by apo(a) results in the formation of elastase-derived apo(a) fragments. These fragments produce a concentration-dependent decrease in the formation of plasmin. Addition of elastase inhibitors to PMNs prevented degradation of apo(a) and partially restored the formation of plasmin. In a similar manner, isolated r-apo(a) fragments were able to produce a 100% decrease in plasmin generation as compared to intact r-apo(a). These data indicate that apo(a) fragments produce a more pronounced inhibition in the generation of cellbound plasmin by uPA than the parent apo(a). These effects of apo(a) and its fragments were neutralised by a monoclonal antibody directed against the lysine-binding site of apo(a). This mechanism may be of biological relevance to the effects of Lp(a) in conditions where PMNs accumulate and release elastase, i.e. thrombus lysis and inflammatory lesions.