Cathepsin-G and Leukocyte Elastase Inactivate Human Tumor Necrosis Factor and Lymphotoxin

Cell Immunol. 1991 Jul;135(2):299-313. doi: 10.1016/0008-8749(91)90275-g.

Abstract

The addition of either cathepsin-G or leukocyte elastase to endotoxin-stimulated human peripheral blood monocytes decreased the immunoreactive tumor necrosis factor (TNF) detected in culture supernatants in a concentration-dependent manner. Both enzymes also induced a loss of supernatant cytolytic activity as determined on the WEHI-164 target cell line. Incubation of recombinant human TNF and lymphotoxin (LT) with either cathepsin-G or leukocyte elastase resulted in a loss of cytokine bioactivity. Examination of enzyme-treated recombinant cytokines by gel electrophoresis revealed that cathepsin-G cleaved LT into a 12.6-kDa fragment and leukocyte elastase fragmented LT into a 14.1-kDa product. On Western blots cathepsin-G and leukocyte elastase degraded TNF into 11- and 7.6-kDa fragments, respectively. Incubating leukocyte elastase with plasma elastase inhibitor alpha-1-antitrypsin prevented the loss of recombinant TNF bioactivity and blocked the degradation of this cytokine. This study suggests that two of the most abundant neutrophil proteases, cathepsin-G and leukocyte elastase, may be important regulators of TNF and LT bioactivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blotting, Western
  • Cathepsin G
  • Cathepsins / pharmacology*
  • Cytotoxicity, Immunologic / drug effects
  • Humans
  • Interleukin-1 / metabolism
  • Leukocyte Elastase
  • Lymphotoxin-alpha / metabolism*
  • Neutrophils / physiology
  • Pancreatic Elastase / pharmacology*
  • Recombinant Proteins / pharmacology
  • Serine Endopeptidases
  • Tumor Necrosis Factor-alpha / metabolism*
  • alpha 1-Antitrypsin / pharmacology

Substances

  • Interleukin-1
  • Lymphotoxin-alpha
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • alpha 1-Antitrypsin
  • Cathepsins
  • Serine Endopeptidases
  • CTSG protein, human
  • Cathepsin G
  • Pancreatic Elastase
  • Leukocyte Elastase