Chemotaxis of human monocyte-derived dendritic cells to complement component C1q is mediated by the receptors gC1qR and cC1qR.
Chemotaxis of human monocyte-derived dendritic cells to complement component C1q is mediated by the receptors gC1qR and cC1qR.
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DOI：
10.1016/j.molimm.2005.07.030
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发表时间：
2006-03
影响因子：
3.6
通讯作者：
Z. Végh;R. Kew;B. Gruber;B. Ghebrehiwet
中科院分区：
文献类型：
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作者：
Z. Végh;R. Kew;B. Gruber;B. Ghebrehiwet
树突状细胞（DC）被募集到炎症部位，在那里它们吞噬并加工抗原，随后呈递给淋巴组织中的T淋巴细胞。几种白细胞化学引诱物及其特异性受体已被证明可诱导DC的迁移。补体蛋白C1 q具有多种免疫功能，包括作为中性粒细胞、嗜酸性粒细胞和肥大细胞的化学引诱物。因此，本研究的目的是确定可溶性C1 q是否可以诱导DC的趋化性。在GM-CSF和IL-4中培养细胞5至7天产生人单核细胞衍生的DC。此外，从第5天至第7天加入LPS以诱导DC成熟。通过流式细胞术、葡聚糖-FITC吞噬作用和同种异体MLR中T细胞增殖评估细胞表面标志物，将细胞分类为未成熟或成熟DC。未成熟DC表达C1 q受体（C1 qR）、gC 1 qR和cC 1 qR/CR，因此，对可溶性C1 q表现出强烈的迁移反应，在10- 50 nM时观察到最大细胞运动。相反，成熟DC既不表达C1 qR，也不向可溶性C1 q的梯度移动。改变C1 q的浓度梯度（棋盘测定）表明，该蛋白质在很大程度上诱导趋化反应。最后，通过使用特异性抗体阻断gC 1 qR和cC 1 qR/CR消除了对C1 q的趋化反应，但对不同的趋化因子C5 a没有影响。这些结果清楚地表明，C1 q功能作为一个趋化因子的未成熟的DC，和迁移介导的连接gC 1 qR和cC 1 qR/CR。
Dendritic cells (DCs) are recruited to inflammatory sites where they phagocytose and process antigens for subsequent presentation to the T lymphocytes in the lymphoid tissue. Several leukocyte chemoattractants and their specific receptors have been shown to induce the migration of DC. The complement protein C1q has multiple immune functions including acting as a chemoattractant for neutrophils, eosinophils and mast cells. Therefore, the objective of this study was to determine if soluble C1q can induce chemotaxis of DC. Culturing cells in GM-CSF and IL-4 for 5 to 7 days generated human monocyte-derived DCs. In addition, LPS was added from day 5 to 7 to induce DC maturation. Cells were classified as either immature or mature DC by assessing the cell surface markers by flow cytometry, phagocytosis of dextran-FITC and T cell proliferation in an allogenic MLR. Immature DCs express the C1q receptors (C1qR), gC1qR and cC1qR/CR and, accordingly, display a vigorous migratory response to soluble C1q with maximal cell movement observed at 10–50nM. In contrast, mature DCs neither express C1qR nor do move to a gradient of soluble C1q. Varying the concentration gradient of C1q (checkerboard assay) showed that the protein largely induces a chemotactic response. Finally, blocking gC1qR and cC1qR/CR by using specific antibodies abolished the chemotactic response to C1q but had no effect on a different chemoattractant C5a. These results clearly demonstrate that C1q functions as a chemotactic factor for immature DC, and migration is mediated through ligation of both gC1qR and cC1qR/CR.