The human neutrophil lipocalin supports the allosteric activation of matrix metalloproteinases

Eur J Biochem. 2001 Apr;268(7):1918-28. doi: 10.1046/j.1432-1327.2001.02066.x.


The human neutrophil lipocalin (HNL), a member of the large family of lipocalins that exhibit various physiological functions, is coexpressed in granulocytes with progelatinase B (MMP-9). Part of it is covalently bound to the proenzyme and therefore may play a possible role in the activation process of promatrix metalloproteinases. We now report that HNL is able to accelerate the direct activation of promatrix metalloproteinases slightly. A significant enhancement of the activity could be demonstrated for the HgCl2- and the plasma kallikrein-induced activation of all three secretory forms of proMMP-9 and of proMMP-8. The same activating effects were exerted by HNL isolated from granulocytes as well as by the recombinant forms expressed by the yeast Pichia pastoris or by Escherichia coli. This demonstrates that the carbohydrate moiety is not essential for the biological activity of HNL. Activation and activity enhancement are obviously mediated by entrapping the remaining N-terminal sequence residues of the partially truncated proenzyme into the hydrophobic binding pocket of the HNL. In conclusion these results document that HNL can exert an enzyme-activating effect in the regulation of inflammatory and pathophysiological responses of granulocytes in the physiological activation of MMPs that have been subject to limited proteolytic processing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins*
  • Amino Acid Sequence
  • Carrier Proteins / administration & dosage
  • Carrier Proteins / isolation & purification
  • Carrier Proteins / pharmacology*
  • Collagenases / isolation & purification
  • Collagenases / metabolism*
  • Dose-Response Relationship, Drug
  • Electrophoresis, Polyacrylamide Gel
  • Enzyme Activation
  • Enzyme Precursors / isolation & purification
  • Enzyme Precursors / metabolism*
  • Escherichia coli
  • Humans
  • Kallikreins / blood
  • Kallikreins / pharmacology
  • Kinetics
  • Lipocalin-2
  • Lipocalins
  • Matrix Metalloproteinase 8 / isolation & purification
  • Matrix Metalloproteinase 8 / metabolism*
  • Matrix Metalloproteinase 9
  • Mercuric Chloride / pharmacology
  • Molecular Sequence Data
  • Neutrophils / enzymology*
  • Neutrophils / metabolism*
  • Oncogene Proteins*
  • Pichia
  • Proto-Oncogene Proteins


  • Acute-Phase Proteins
  • Carrier Proteins
  • Enzyme Precursors
  • LCN2 protein, human
  • Lipocalin-2
  • Lipocalins
  • Oncogene Proteins
  • Proto-Oncogene Proteins
  • Mercuric Chloride
  • Kallikreins
  • Collagenases
  • pro-matrix metalloproteinase 9
  • Matrix Metalloproteinase 8
  • Matrix Metalloproteinase 9