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

Proteinase-activated receptor-2 up-regulation by Fcgamma-receptor activation in human neutrophils.
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DOI:
10.1096/fj.09-146167
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发表时间:
2010-06
期刊:
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子:
--
通讯作者:
Pouliot M
Pouliot M
中科院分区:
其他
文献类型:
--
作者:
St-Onge M;Lagarde S;Laflamme C;Rollet-Labelle E;Marois L;Naccache PH;Pouliot M

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我们揭示了与炎症和痛觉过敏相关的蛋白酶激活受体(PAR)家族在人粒细胞中的表达和功能。静息细胞表达组成水平的PAR-2和PAR-3 mRNA,但不表达PAR-1或PAR-4。基于流式细胞术,调理菌(opsonized bacteria, Bop)刺激以浓度依赖和时间依赖的方式特异性上调细胞表面PAR-2的表达,独立于转录或从头蛋白合成。原生颗粒被确定为预制PAR-2的来源,可以很容易地在与质膜融合时在表面动员。通过测量细胞内钙浓度的变化,细胞对PAR-2激活的反应在PAR-2上调的细胞中增强。细胞表面PAR-2和细胞反应性的增加特异性地依赖于免疫球蛋白(Ig)结合受体的参与。总之,我们的研究结果表明,细胞内颗粒的动员响应于ig受体的激活,上调PAR-2表面表达,并使中性粒细胞对蛋白酶活性更敏感。这种对PAR-2激活的增强反应表明,疼痛和炎症之间的分子交流可能比以前认为的更重要。
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.
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