Endotoxin-induced production of plasminogen activator inhibitor by human monocytes is autonomous and can be inhibited by lipid X

Blood. 1989 Jun;73(8):2188-95.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Communication
  • Dose-Response Relationship, Immunologic
  • Endotoxins / antagonists & inhibitors
  • Endotoxins / pharmacology*
  • Glycolipids / pharmacology*
  • Glycoproteins / antagonists & inhibitors
  • Glycoproteins / pharmacology*
  • Humans
  • Immunoenzyme Techniques
  • Lipopolysaccharides / antagonists & inhibitors
  • Lipopolysaccharides / pharmacology
  • Lymphocytes / physiology
  • Monocytes / metabolism*
  • Monocytes / physiology
  • Plasminogen Inactivators
  • Staining and Labeling
  • Thromboplastin / biosynthesis

Substances

  • Endotoxins
  • Glycolipids
  • Glycoproteins
  • Lipopolysaccharides
  • Plasminogen Inactivators
  • lipid X
  • Thromboplastin