Regulation of plasminogen receptor expression on human monocytes and monocytoid cell lines.

Abstract

Abstract. The capacity of human monocytoid cell lines and peripheral blood monocytes to modulate their expression of plasminogen receptors has been assessed. After PMA stimulation, THP-1 or U937 monocytoid cells were separated into adherent and nonadherent populations. Plasminogen bound to adherent cells with similar capacity and affinity as to nonstimulated cells. In contrast, the nonadherent cells bound plasminogen with 5-17-fold higher capacity (without a change in affinity). This increase was selective as urokinase bound with similar affinity and capacity to the adherent and nonadherent populations. Upregulation of plasminogen receptors on the nonadherent monocytoid cells was rapid, detectable within 30 min, and reversible, adhesion of the nonadherent cells resulted in a sixfold decrease in plasminogen binding within 90 min. The increase in plasminogen binding to the nonadherent cells was associated with a marked increase in their capacity to generate plasmin activity from cell-bound plasminogen.PMA stimulation of human peripheral blood monocytes increased their expression of plasminogen receptors by two-to fourfold. This increase was observed in both adherent and nonadherent monocytes. Freshly isolated monocytes maximally bound 5.0 x 1@ plasminogen molecules per cell, whereas monocytes cultured for 18 h or more maximally bound 1.7 × 107 molecules per cell, a 30-fold difference in receptor number. These results indicate that both monocytes and monocytoid cell lines can rapidly and markedly regulate their expression of plasminogen binding sites. As enhanced plasminogen binding is correlated with an increased capacity to generate plasmin, an enzyme with broad substrate recognition, modulation of plasminogen receptors may have profound functional consequences.

Processing of chromogranin A by plasmin provides a novel mechanism for regulating catecholamine secretion

“…The t-PA bound to the cells, and the binding was 78% inhibited by unlabeled t-PA, as well as by arginine and EACA, which also inhibits the binding of t-PA to other cell types (32).…”

“…Diisopropyl fluorophosphate (DFP) was used to inactivate t-PA, which was iodinated using the lactoperoxidase method, as described elsewhere (32).…”

Structure and function of human plasma carboxypeptidase N, the anaphylatoxin inactivator

“…By decreasing cellular plasminogen binding [78], CPN can reduce plasmin-dependent extracellular matrix degradation and cellular migration [77,81]. For example, freshly isolated monocytes, exposed to CPN in the plasma, bind about 30-fold less plasminogen than monocytes cultured for 18 h or longer [82]. As described above, plasmin can cleave both subunits of CPN, causing increased activity; proteolytically cleaved CPN is also more effective in reducing cellular plasminogen binding than native CPN [78].…”

Inhibition of plasminogen activation by apo(a): role of carboxyl-terminal lysines and identification of inhibitory domains in apo(a)

“…Both tPA and uPA have been shown to be expressed in a variety of cell types, including endothelial cells for tPA ( 51 ) and lung, kidney, and several tumor cell lines for uPA ( 52,53 ). It has been shown that tPA can directly bind to various cell types other than endothelial cells, such as platelets, monocytes, and monocytoid cells ( 30,39,54,55 ). Lp(a) was reported to inhibit plasminogen activation on the surface of resting platelets by inhibiting plasminogen and tPA binding ( 56 ).…”