Endotoxin-induced production of plasminogen activator inhibitor by human monocytes is autonomous and can be inhibited by lipid X.
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.
Schwartz
B S
BS
Department of Medicine, University of Wisconsin, Madison.
Monroe
M C
MC
Bradshaw
J D
JD
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
D004731:Endotoxins; D006017:Glycolipids; D006023:Glycoproteins; D008070:Lipopolysaccharides; D015849:Plasminogen Inactivators; C044283:lipid X; D013925:Thromboplastin