INTERACTION OF LP(A) WITH PLASMINOGEN BINDING-SITES ON CELLS

Lp(a) competes with plasminogen for binding to cells but it is not kno wn whether this competition is due to the ability of Lp(a) to interact directly with plasminogen receptors. In the present study, we demonst rate that Lp(a) can interact directly with plasminogen binding sites o n monocytoid U937 cells and endothelial cells. The interaction of Lp(a ) with these sites was time dependent, specific, saturable, divalent i on independent and temperature sensitive, characteristics of plasminog en binding to these sites. The affinity of plasminogen and Lp(a) for t hese sites also was similar (K-d = 1-3 mu M ), but Lp(a) bound to fewe r sites (similar to 10-fold less). Both gangliosides and cell surface proteins with car boxy-terminal lysyl residues, including enolase, a c andidate plasminogen receptor, inhibited Lp(a) binding to U937 cells. Additionally, Lp(a) interacted with low affinity lipoprotein binding s ites on these cells which also recognized LDL and HDL. The ability of Lp(a) to interact with sites on cells that recognize plasminogen may c ontribute to the pathogenetic consequences of high levels of circulati ng Lp(a).