IgA1 protease from Neisseria gonorrhoeae inhibits TNFalpha-mediated apoptosis of human monocytic cells

FEBS Lett. 2000 Apr 28;472(2-3):287-92. doi: 10.1016/s0014-5793(00)01478-2.

Abstract

The modulation of programmed cell death is a common theme in the patho-physiology of inflammation and infectious disease. The synthesis and secretion of an IgA1 protease is strictly associated with virulence of the Neisseria species. Here, we report on the inhibition of tumor necrosis factor alpha (TNFalpha)-mediated apoptosis of the human myelo-monocytic cell line U937 by highly purified IgA1 protease. Apoptosis was verified by the cell surface exposure of phosphatidyl serine and by terminal transferase mediated end-labeling of fragmented DNA. Interestingly, IgA1 protease specifically cleaved the TNF receptor II (TNF-RII) on the surface of intact cells whereas TNF-RI was not affected by the enzyme. Therefore, inhibition of TNFalpha-mediated apoptosis might be correlated to specific cleavage of the TNF-RII by neisserial IgA1 protease.

MeSH terms

  • Antigens, CD / metabolism
  • Apoptosis / drug effects*
  • Biological Transport
  • DNA Fragmentation
  • Humans
  • Monocytes / cytology
  • Monocytes / drug effects
  • Monocytes / metabolism
  • Neisseria gonorrhoeae / enzymology*
  • Phosphatidylserines / metabolism
  • Receptors, Tumor Necrosis Factor / metabolism
  • Receptors, Tumor Necrosis Factor, Type II
  • Serine Endopeptidases / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology
  • U937 Cells

Substances

  • Antigens, CD
  • Phosphatidylserines
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type II
  • Tumor Necrosis Factor-alpha
  • Serine Endopeptidases
  • IgA-specific serine endopeptidase