title: Endotoxin-induced production of plasminogen activator inhibitor by human monocytes is autonomous and can be inhibited by lipid X.
abstract: Peripheral blood mononuclear cells (PBMs) produce both tissue factor and plasminogen activator inhibitor type 2 (PAI-2) in response to gram-negative bacterial lipopolysaccharide (LPS). The cellular roles in the tissue factor response have been previously elucidated, and we now report those roles in PAI-2 production. Monocytes are the only cells among LPS-stimulated PBMs that produce PAI-2 as assessed by measurement of PAI-2 activity and antigen. Concomitant immunohistochemistry demonstrated that monocytes contain PAI-2, with a greater number staining positively and more intensely after exposure to LPS. LPS-stimulated monocytes produced increased amounts of PAI-2 with or without addition of lymphocytes. Lymphocytes prestimulated with LPS and then washed did not induce PAI-2 production in monocytes to which they were added. Lipid X, a precursor in the biosynthetic pathway of lipid A and LPS, was able to inhibit LPS induction of monocyte PAI-2 in a dose-dependent manner. This inhibition was not due to cellular toxicity, the phospholipidlike nature of lipid X, interference with the PAI-2 assay, or monocyte production of a substance interfering with PAI-2. Lipid X was an effective inhibitor of PAI-2 production even when added up to 30 minutes after LPS.
authors: Department of Medicine, University of Wisconsin, Madison.
authors: B S
authors: BS
authors: Schwartz
authors: M C
authors: MC
authors: Monroe
authors: J D
authors: JD
authors: Bradshaw
mesh_terms: D002450:Cell Communication; D004306:Dose-Response Relationship, Immunologic; D004731:Endotoxins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006017:Glycolipids / Q000494:pharmacology*; D006023:Glycoproteins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006801:Humans; D007124:Immunoenzyme Techniques; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008214:Lymphocytes / Q000502:physiology; D009000:Monocytes / Q000378:metabolism* / Q000502:physiology; D015849:Plasminogen Inactivators; D013194:Staining and Labeling; D013925:Thromboplastin / Q000096:biosynthesis
chemical_list: D004731:Endotoxins; D006017:Glycolipids; D006023:Glycoproteins; D008070:Lipopolysaccharides; D015849:Plasminogen Inactivators; C044283:lipid X; D013925:Thromboplastin