TY - JOUR
T1 - Role of proteinase-activated receptor-2 in anti-bacterial and immunomodulatory effects of interferon-γ on human neutrophils and monocytes
AU - Shpacovitch, Victoria M.
AU - Feld, Micha
AU - Holzinger, Dirk
AU - Kido, Makiko
AU - Hollenberg, Morley D.
AU - Levi-Schaffer, Francesca
AU - Vergnolle, Nathalie
AU - Ludwig, Stephan
AU - Roth, Johannes
AU - Luger, Thomas
AU - Steinhoff, Martin
PY - 2011/7
Y1 - 2011/7
N2 - 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.
AB - 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.
KW - Innate immunity
KW - Monocyte chemoattractant protein-1
KW - Phagocytosis
KW - Proteinase-activated receptor
KW - Staphylococcus aureus
UR - http://www.scopus.com/inward/record.url?scp=79957838438&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2567.2011.03443.x
DO - 10.1111/j.1365-2567.2011.03443.x
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C2 - 21501162
AN - SCOPUS:79957838438
SN - 0019-2805
VL - 133
SP - 329
EP - 339
JO - Immunology
JF - Immunology
IS - 3
ER -
