Interaction between CD177 and platelet endothelial cell adhesion molecule-1 downregulates membrane-bound proteinase-3 (PR3) expression on neutrophils and attenuates neutrophil activation induced by PR3-ANCA.
Interaction between CD177 and platelet endothelial cell adhesion molecule-1 downregulates membrane-bound proteinase-3 (PR3) expression on neutrophils and attenuates neutrophil activation induced by PR3-ANCA.
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CD177 和血小板内皮细胞粘附分子 1 之间的相互作用下调中性粒细胞上膜结合蛋白酶 3 (PR3) 的表达并减弱 PR3-ANCA 诱导的中性粒细胞活化
DOI：
10.1186/s13075-018-1710-0
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发表时间：
2018-09-20
影响因子：
4.9
通讯作者：
Zhao MH
中科院分区：
文献类型：
--
作者：
Deng H;Hu N;Wang C;Chen M;Zhao MH
研究背景最近的一项研究发现，CD 177在中性粒细胞亚群中作为膜结合蛋白酶3（mPR 3）的受体。此外，CD 177已被鉴定为内皮细胞血小板内皮细胞粘附分子-1（PECAM-1）的高亲和力异嗜性结合伴侣。本研究旨在探讨PECAM-1和CD 177之间的相互作用是否可以影响mPR 3的表达以及PR 3-抗神经元胞质抗体（ANCA）诱导的中性粒细胞活化和肾小球内皮细胞（GEnC）损伤。用二氢罗丹明（DHR）法和ELISA法检测PECAM-1对PR 3-ANCA阳性免疫球蛋白（IG）Gs诱导的中性粒细胞活化和GEnC损伤的影响。CD 177阴性的中性粒细胞选择磁性细胞分选（MACS），和PECAM-1对CD 177阴性和混合中性粒细胞的抑制作用进行了探讨，通过测量中性粒细胞脱粒。在与PECAM-1预孵育的中性粒细胞中，mPR 3的表达以剂量依赖性方式显著降低。因此，在重组人肿瘤坏死因子-α（TNF-α）致敏的中性粒细胞中，PR 3-ANCA阳性IgG诱导的呼吸爆发和脱粒水平在PECAM-1预孵育后显著降低（440.6 ± 123.0对511.4 ± 95.5，p < 0.05; 3155.0 ± 1733.0对5903.0 ± 717.5ng/ml，p< 0.05）。在与PR 3-ANCA阳性IgG孵育的CD 177阴性中性粒细胞中，与PECAM-1预孵育未显著改变脱粒水平。而在混合型中性粒细胞中，PECAM-1显著降低PR 3-ANCA阳性IgG诱导的脱颗粒水平（1015.9 ± 229.2%vs.1725.2 ± 412.4%，p < 0.01）。此外，用TNF-α致敏的中性粒细胞与PECAM-1预孵育，用致敏的中性粒细胞加PR 3-ANCA阳性IgG处理的GEnC上清液中可溶性细胞间粘附分子-1（sICAM-1）（内皮细胞活化和损伤的标志物）的水平显著减弱结论PECAM-1可降低中性粒细胞mPR 3表达水平，从而减轻PR 3-ANCA阳性IgG诱导的中性粒细胞活化和随后的GEnC损伤。
BackgroundA recent study found that CD177 served as a receptor of membrane-bound proteinase-3 (mPR3) in a subset of neutrophils. Furthermore, CD177 has been identified as a high-affinity heterophilic binding partner for the endothelial cell platelet endothelial cell adhesion molecule-1 (PECAM-1). The current study aimed to investigate whether the interaction between PECAM-1 and CD177 could influence mPR3 expression as well as PR3-antineutrophil cytoplasmic antibody (ANCA)-induced neutrophil activation and glomerular endothelial cell (GEnC) injury.MethodsThe effect of interaction between CD177 and PECAM-1 on mPR3 expression was explored by enzyme-linked immunosorbent assay (ELISA) and flow cytometry. The effect of PECAM-1 on neutrophil activation and GEnC injury induced by PR3-ANCA-positive immunoglobulin (Ig)Gs was evaluated by dihydrorhodamine (DHR) assay and ELISA. CD177-negative neutrophils were selected by magnetic cell sorting (MACS), and the inhibitory effect of PECAM-1 on CD177-negative and mixed neutrophils was explored by measuring neutrophil degranulation.ResultsThe level of specific interaction between CD177 and PECAM-1 was elevated with increasing CD177 concentration. The expression of mPR3 significantly decreased in neutrophils preincubated with PECAM-1 in a dose-dependent manner. Consistently, the levels of respiratory burst and degranulation induced by PR3-ANCA-positive IgGs in recombinant human tumor necrosis factor-alpha (TNF-α)-primed neutrophils was significantly reduced by preincubation with PECAM-1 (440.6 ± 123.0 vs. 511.4 ± 95.5,p< 0.05; and 3155.0 ± 1733.0 ng/ml vs. 5903.0 ± 717.5 ng/ml,p< 0.05, respectively). In CD177-negative neutrophils incubated with PR3-ANCA-positive IgGs, the level of degranulation was not significantly changed by preincubation with PECAM-1. However, in mixed neutrophils, PECAM-1 significantly decreased the level of degranulation induced by PR3-ANCA-positive IgGs (1015.9 ± 229.2% vs. 1725.2 ± 412.4%,p< 0.01). Furthermore, with preincubation of TNF-α-primed neutrophils with PECAM-1, the level of soluble intercellular cell adhesion molecule-1 (sICAM-1), a marker of endothelial cell activation and injury, in the supernatant of GEnCs treated with primed neutrophils plus PR3-ANCA-positive IgGs was significantly attenuated (112.7 ± 24.2 pg/ml vs. 167.5 ± 27.7 pg/ml,p< 0.05).ConclusionsPECAM-1 can decrease the level of mPR3 expression on neutrophils, resulting in attenuation of neutrophil activation and subsequent GEnC injury induced by PR3-ANCA-positive IgGs.
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影响因子：
20.3
作者：
Bai, Ming;Grieshaber-Bouyer, Ricardo;Nigrovic, Peter A.
通讯作者：
Nigrovic, Peter A.
影响因子：
5.5
作者：
Nourshargh, Sussan;Krombach, Fritz;Dejana, Elisabetta
通讯作者：
Dejana, Elisabetta
影响因子：
5.2
作者：
Page AV;Liles WC
通讯作者：
Liles WC
影响因子：
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作者：
Jennette, J. C.;Falk, R. J.;Watts, R. A.
通讯作者：
Watts, R. A.
人内皮细胞限制的外部处置的浆膜蛋白，富含细胞间连接。
影响因子：
15.3
作者：
Muller, W A;Ratti, C M;McDonnell, S L;Cohn, Z A
通讯作者：
Cohn, Z A