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Proteinase‐activated receptor‐2 up‐regulation by Fcγ‐receptor activation in human neutrophils
Author(s) -
StOnge Mireille,
Lagarde Ste´phanie,
Laflamme Cynthia,
RolletLabelle Emmanuelle,
Marois Louis,
Naccache Paul H.,
Pouliot Marc
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.09-146167
Subject(s) - receptor , microbiology and biotechnology , intracellular , cell surface receptor , flow cytometry , inflammation , biology , receptor expression , chemistry , immunology , biochemistry
We shed new light on the expression and function of the proteinase‐activated receptor (PAR) family, associated with inflammation and hyperalgesia, in human granulocytes. Resting cells expressed constitutive levels of PAR‐2 and PAR‐3 mRNA but not PAR‐1 or PAR‐4. Based on flow cytometry, stimulation with opsonized bacteria ( Bop ) specifically up‐regulated cell surface expression of PAR‐2 in a concentration‐dependent and time‐dependent manner, independent of transcription or de novo protein synthesis. Primary granules were identified as a source of preformed PAR‐2 that can readily be mobilized at the surface on fusion with the plasma membrane. Cellular response to PAR‐2 activation, measured as changes in intracellular calcium concentration, was enhanced in PAR‐2 up‐regulated cells. Increase of cell‐surface PAR‐2 and of cell responsiveness were dependent specifically on the engagement of immunoglobulin (Ig)‐binding receptors. Together, our results reveal that mobilization of intracellular granules, in response to Ig‐receptor activation, up‐regulates PAR‐2 surface expression and makes neutrophils more responsive to proteinase activity. This enhanced response to PAR‐2 activation indicates that molecular communication between pain and inflammation may be more important than previously believed.—St‐Onge, M., Lagarde, S., Laflamme, C, Rollet‐Labelle, E., Marois, L., Naccache, P. H., Pouliot, M. Proteinase‐activated receptor‐2 up‐regulation by Fcγ‐receptor activation in human neutrophils. FASEB J . 24, 2116–2125 (2010). www.fasebj.org