Proteinase-activated receptor-2 up-regulation by Fcγ-receptor activation in human neutrophils

被引:16
作者
St-Onge, Mireille [1 ]
Lagarde, Stephanie [1 ]
Laflamme, Cynthia [1 ]
Rollet-Labelle, Emmanuelle [1 ]
Marois, Louis [1 ]
Naccache, Paul H. [1 ]
Pouliot, Marc [1 ]
机构
[1] Univ Laval, Ctr Rech Rhumatol & Immunol, CHU Quebec, Dept Microbiol Infectiol & Immunol,Fac Med, Quebec City, PQ G1K 7P4, Canada
基金
美国国家卫生研究院; 加拿大健康研究院;
关键词
inflammation; polymorphonuclear leukocytes; PARs; primary granules; EPITHELIAL-CELLS; PROINFLAMMATORY CYTOKINES; MEDIATED PHAGOCYTOSIS; ADHESION MOLECULES; GENE-EXPRESSION; URATE CRYSTALS; IN-VIVO; INFLAMMATION; MIGRATION; THROMBIN;
D O I
10.1096/fj.09-146167
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 upregulation by Fc gamma-receptor activation in human neutrophils. FASEB J. 24, 2116-2125 (2010). www.fasebj.org
引用
收藏
页码:2116 / 2125
页数:10
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