Lactoferrin Is an Allosteric Enhancer of the Proteolytic Activity of Cathepsin G

Steffen Eipper, Robin Steiner, Adam Lesner, Marcin Sienczyk, David Palesch, Marc-Eric Halatsch, Ewa Zaczynska, Christopher Heim, Marcus D Hartmann, Michal Zimecki, Christian Rainer Wirtz, Timo Burster

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Protease-mediated degradation of proteins is critical in a plethora of physiological processes. Neutrophils secrete serine proteases including cathepsin G (CatG), neutrophile elastase (NE), and proteinase 3 (PR3) together with lactoferrin (LF) as a first cellular immune response against pathogens. Here, we demonstrate that LF increases the catalytic activity of CatG at physiological concentration, with its highest enhancing capacity under acidic (pH 5.0) conditions, and broadens the substrate selectivity of CatG. On a functional level, the enzymatic activity of CatG was increased in the presence of LF in granulocyte-derived supernatant. Furthermore, LF enhanced CatG-induced activation of platelets as determined by cell surface expression of CD62P. Consequently, LF-mediated enhancement of CatG activity might promote innate immunity during acute inflammation.

Original languageEnglish
Pages (from-to)e0151509
JournalPLoS One
Volume11
Issue number3
DOIs
Publication statusPublished - 2016
Externally publishedYes

Keywords

  • Allosteric Regulation
  • Biocatalysis
  • Cathepsin G
  • Culture Media, Conditioned
  • Electrophoresis, Polyacrylamide Gel
  • Enzyme Activation
  • Granulocytes
  • Humans
  • Hydrogen-Ion Concentration
  • Immunity, Innate
  • Immunoblotting
  • Inflammation
  • Lactoferrin
  • Leukocyte Elastase
  • Platelet Activation
  • Proteolysis
  • Substrate Specificity
  • Journal Article
  • Research Support, Non-U.S. Gov't

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  • Cite this

    Eipper, S., Steiner, R., Lesner, A., Sienczyk, M., Palesch, D., Halatsch, M-E., Zaczynska, E., Heim, C., Hartmann, M. D., Zimecki, M., Wirtz, C. R., & Burster, T. (2016). Lactoferrin Is an Allosteric Enhancer of the Proteolytic Activity of Cathepsin G. PLoS One, 11(3), e0151509. https://doi.org/10.1371/journal.pone.0151509