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.
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.
Mireille
M
St-Onge
Stéphanie
S
Lagarde
Cynthia
C
Laflamme
Emmanuelle
E
Rollet-Labelle
Louis
L
Marois
Paul H
PH
Naccache
Marc
M
Pouliot
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