Secretory leukocyte protease inhibitor: a macrophage product induced by and antagonistic to bacterial lipopolysaccharide

Cell. 1997 Feb 7;88(3):417-26. doi: 10.1016/s0092-8674(00)81880-2.

Abstract

To explore regulation of potentially lethal responses to bacterial lipopolysaccharide (LPS), we used differential display under LPS-free conditions to compare macrophage cell lines from two strains of mice congenic for a locus affecting LPS sensitivity. LPS-hyporesponsive cells, primary macrophages, and polymorphonuclear leukocytes transcribed secretory leukocyte protease inhibitor (SLPI), a known epithelial cell-derived inhibitor of leukocyte serine proteases. Transfection of macrophages with SLPI suppressed LPS-induced activation of NF-kappa B and production of nitric oxide and TNF alpha. The ability of interferon-gamma (IFN gamma) to restore LPS responsiveness is a hallmark of the LPS-hyporesponsive phenotype. IFN gamma suppressed expression of SLPI and restored LPS responsiveness to SLPI-producing cells. Thus, SLPI is an LPS-induced IFN gamma-suppressible phagocyte product that serves to inhibit LPS responses.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Differentiation / drug effects
  • Cell Line
  • Cloning, Molecular
  • Female
  • Immunosuppressive Agents / pharmacology
  • Interferon-gamma / pharmacology
  • Lipopolysaccharides / antagonists & inhibitors*
  • Lipopolysaccharides / pharmacology*
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Mice
  • Mice, Inbred C3H
  • Molecular Sequence Data
  • Neutrophils / metabolism
  • Organ Specificity
  • Protein Biosynthesis*
  • Proteinase Inhibitory Proteins, Secretory
  • Proteins / genetics
  • Proteins / pharmacology*
  • Secretory Leukocyte Peptidase Inhibitor
  • Serine Proteinase Inhibitors / biosynthesis*
  • Serine Proteinase Inhibitors / genetics
  • Serine Proteinase Inhibitors / pharmacology*

Substances

  • Immunosuppressive Agents
  • Lipopolysaccharides
  • Proteinase Inhibitory Proteins, Secretory
  • Proteins
  • Secretory Leukocyte Peptidase Inhibitor
  • Serine Proteinase Inhibitors
  • Slpi protein, mouse
  • Interferon-gamma

Associated data

  • GENBANK/U73004
  • GENBANK/X04502