Neutrophil-derived azurocidin cleaves insulin-like growth factor-binding protein-1, -2 and -4

Growth Horm IGF Res. 2011 Jun;21(3):167-73. doi: 10.1016/j.ghir.2011.04.003. Epub 2011 May 7.

Abstract

Objective: Azurocidin is an important inflammatory mediator and considered to be an inactive serine protease homologue. It has previously been reported that azurocidin is a possible IGFBP-1 specific protease; however, the protease-activity of azurocidin was not isolated in its active form. The aim of this study was to determine the effect of neutrophil-derived azurocidin on the six different IGFBPs, focusing especially on IGFBP-1.

Methods: IGFBPs were incubated with azurocidin in phosphate-buffered saline for 2 h and proteolysis was studied by SDS-PAGE. Analysis of azurocidin was performed by MALDI-TOF peptide mass fingerprint and MALDI-TOF/TOF peptide sequencing.

Results: The neutrophil-derived preparation of azurocidin cleaved IGFBP-1, IGFBP-2 and IGFBP-4. IGFBP-1 bound to IGF-I was also degraded whereas IGF-II was shown to have an inhibitory effect on proteolysis of IGFBP-1. The proteolytically active preparation of neutrophil-derived azurocidin was found to be glycosylated and determined to be 31 kDa by SDS-PAGE.

Conclusions: Our results indicate that the neutrophil-derived preparation of azurocidin contains a protease activity which cleaves IGFBP-1, IGFBP-2 and IGFBP-4. These findings are of interest since both IGFBP-1 and azurocidin increase during inflammation. The effect of azurocidin on IGFBP- and IGF-activity needs to be further investigated.

MeSH terms

  • Antimicrobial Cationic Peptides / metabolism*
  • Blood Proteins / metabolism*
  • Blotting, Western
  • Carrier Proteins / metabolism*
  • Insulin-Like Growth Factor Binding Protein 1 / metabolism*
  • Insulin-Like Growth Factor Binding Protein 2 / metabolism*
  • Insulin-Like Growth Factor Binding Protein 4 / metabolism*
  • Neutrophils / metabolism*
  • Peptides / chemistry
  • Peptides / metabolism
  • Phosphorylation
  • Protein Isoforms / metabolism
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • AZU1 protein, human
  • Antimicrobial Cationic Peptides
  • Blood Proteins
  • Carrier Proteins
  • Insulin-Like Growth Factor Binding Protein 1
  • Insulin-Like Growth Factor Binding Protein 2
  • Insulin-Like Growth Factor Binding Protein 4
  • Peptides
  • Protein Isoforms