Pharmacological modulation of plasminogen activator secretion by P388D1 cell line

P388D1 is a murine macrophage cell line which spontaneously secretes plasminogen activator (PA; activated function) and lysozyme (LYS; constitutive function). Compounds which decrease PA secretion without affecting LYS secretion have potential as "down-regulators" of macrophage function and, hence, of the immune system. Glucocorticoids (e.g., dexamethasone, IC50 less than 0.01 microM) and auranofin (IC50 = 1 microM) are positive in this model. In contrast, cyclooxygenase inhibitors (indomethacin, ibuprofen and piroxicam, all at 1 microM) boost PA secretion; lipoxygenase inhibitors (REV-5901, NDGA and piriprost, all at 10 microM) have little or no effect. Dexamethasone, but not auranofin, induces a urokinase-inhibitory activity which elutes between 0.13 and 0.19 M NaCl upon anion exchange HPLC (TSK-DEAE-5-PW). Fibrin overlay following SDS-PAGE of the HPLC peak reveals a urokinase-inhibitory band at approximately 90 Kd.