Role of proteinase-activated receptor-2 in anti-bacterial and immunomodulatory effects of interferon-γ on human neutrophils and monocytes

Victoria M. Shpacovitch*, Micha Feld, Dirk Holzinger, Makiko Kido, Morley D. Hollenberg, Francesca Levi-Schaffer, Nathalie Vergnolle, Stephan Ludwig, Johannes Roth, Thomas Luger, Martin Steinhoff

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Recent studies show that proteinase-activated receptor-2 (PAR2) contributes to the development of inflammatory responses. However, investigations into the precise role of PAR2 activation in the anti-microbial defence of human leucocytes are just beginning. We therefore evaluated the contribution of PAR2 to the anti-microbial response of isolated human innate immune cells. We found that PAR2 agonist, acting alone, enhances phagocytosis of Staphylococcus aureus and killing of Escherichia coli by human leucocytes, and that the magnitude of the effect is similar to that of interferon-γ (IFN-γ). However, co-application of PAR2-cAP and IFN-γ did not enhance the phagocytic and bacteria-killing activity of leucocytes beyond that triggered by either agonist alone. On the other hand, IFN-γ enhances PAR2 agonist-induced monocyte chemoattractant protein 1 (MCP-1) secretion by human neutrophils and monocytes. Furthermore, phosphoinositide-3 kinase and janus kinase molecules are involved in the synergistic effect of PAR2 agonist and IFN-γ on MCP-1 secretion. Our findings suggest a potentially protective role of PAR2 agonists in the anti-microbial defence established by human monocytes and neutrophils.

Original languageAmerican English
Pages (from-to)329-339
Number of pages11
JournalImmunology
Volume133
Issue number3
DOIs
StatePublished - Jul 2011

Keywords

  • Innate immunity
  • Monocyte chemoattractant protein-1
  • Phagocytosis
  • Proteinase-activated receptor
  • Staphylococcus aureus

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