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

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.