Proteinase-activated receptor-2 up-regulation by Fcgamma-receptor activation in human neutrophils.
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
Mireille
M
Centre de Recherche en Rhumatologie et Immunologie du Centre Hospitalier Universitaire de Québec, Department of Microbiology-Infectiology and Immunology, Faculty of Medicine, Laval University, Quebec, Canada.
Lagarde
Stéphanie
S
Laflamme
Cynthia
C
Rollet-Labelle
Emmanuelle
E
Marois
Louis
L
Naccache
Paul H
PH
Pouliot
Marc
M
D015153:Blotting, Western; D020013:Calcium Signaling; D002478:Cells, Cultured; D006098:Granulocytes / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D006801:Humans; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044464:Receptor, PAR-2 / Q000235:genetics / Q000378:metabolism*; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012480:Salmonella Infections / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D012486:Salmonella typhimurium / Q000472:pathogenicity; D015398:Signal Transduction; D015854:Up-Regulation
C489017:FCGR1A protein, human; D012333:RNA, Messenger; D044464:Receptor, PAR-2; D017452:Receptors, IgG