Regulation of the plasminogen activator inhibitor-2 (PAI-2) gene in murine macrophages. Demonstration of a novel pattern of responsiveness to bacterial endotoxin

We investigate the regulation of plasminogen activator inhibitor-2 (PAI-2) inn murine macrophages. PAI-2 mRNA Tvas inducible By bacterial lipopolysaccharide (LPS) in primary cells and macrophage-like cell Lines. Evidence is presented for a role for autocrine factors, including cyclooxygenase products but not the cytokines tumor necrosis factor alpha or interferon-beta (IFN-beta), PAI-2 mRNA levels generally varied inversely front those of its target, urokinase-type plasminogen activator (uPA), and the macrophage growth factor CSF-1, which induces uPA, inhibited PAI-2 expression hn cells treated subsequently with LPS. Expression of PAI-2 Tvas distinct from that of other LPS-inducible genes in terms of induction time course, LPS dose response, and sensitivity to co-stimulation with IFN-gamma, induction of PAI-2 mRNA in subclones of the cell hue RAW 264 was not uniform, reflecting heterogeneous expression in the parent line. The expression pattern of PAI-2 is discussed inn terms of a possible role in LPS-induced pathology such as septicemia.