Expression of CCR5 receptors on Reed-Sternberg cells and Hodgkin lymphoma cell lines: Involvement of CCL5/Rantes in tumor cell growth and microenvironmental interactions
Expression of CCR5 receptors on Reed-Sternberg cells and Hodgkin lymphoma cell lines: Involvement of CCL5/Rantes in tumor cell growth and microenvironmental interactions
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DOI：
10.1002/ijc.23119
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发表时间：
2008-02-15
影响因子：
6.4
通讯作者：
Colombatti, Alfonso
中科院分区：
文献类型：
--
作者：
Aldinucci, Donatella;Lorenzon, Debora;Colombatti, Alfonso
最近已经记录了Hodgkin（H）和Reed-Sternberg（RS）细胞表达CCL 5/Rantes。在本研究中，我们证明了CCL 5受体（CCR 5）的组成型表达霍奇金淋巴瘤（HL）衍生的细胞系（即L-428，KM-H2，L-1236和L-540）所示的免疫组织化学，流式细胞术和蛋白质印迹法，也检测到免疫组织化学对原代H-RS细胞从淋巴结组织。sCD 40 L从未显著影响CCR 5表达，而短时间暴露于阿霉素下调其表达。HL细胞系上的CCR 5受体具有功能活性，因为中和性抗CCL 5单克隆抗体抑制HL衍生细胞系的基础增殖，并且重组CCR 5配体（CCL 3/Mip-1 α、CCL 4/Mipl β和CCL 5/Rantes）增加其克隆形成生长。通过CD 40结合以及通过在来自HL涉及的淋巴结（HLF）的原代基质成纤维细胞上共培养L-1236细胞来刺激L-1236、L-428和KM-H2细胞的CCL 5分泌。共培养实验表明，H-RS细胞的直接接触诱导HLF细胞产生CCL 5。来自L-1236、L-428和KM-H2细胞的上清液刺激纯化的CD 4 + T细胞和嗜酸性粒细胞的体外迁移。HL-细胞系上清液的迁移反应仅被抗CCL 5抗体部分中和（CD 4+细胞：70%;嗜酸性粒细胞：36%），加强了HL组织中非恶性反应细胞募集中涉及多种趋化因子的观点。两者合计，我们的研究结果表明，可能参与的CCR 5/CCR 5-配体信号调节H-RS细胞的生长和HL的典型组织微环境的形成/维持。(C)2007 Wiley-Liss，Inc.
The expression of CCL5/Rantes by Hodgkin (H) and Reed-Sternberg (RS) cells has been recently documented. In the present study we demonstrated that the CCL5 receptor (CCR5) is constitutively expressed by Hodgkin Lymphoma (HL)-derived cell lines (i.e. L-428, KM-H2, L-1236 and L-540) as shown by immunohistochemistry, flow cytometry and western blotting and also detected by immunobistochemistry on primary H-RS cells from lymph node tissues. sCD40L never significantly affected CCR5 expression, whereas a short exposure to doxorubicin down regulated its expression. CCR5 receptors on HL cell lines were functionally active, since neutralizing anti-CCL5 monoclonal antibodies inhibited basal proliferation of HL-derived cell lines and recombinant CCR5 ligands (CCL3/Mip-1 alpha, CCL4/Mipl beta and CCL5/Rantes) increased their clonogenic growth. CCL5 secretion by L-1236, L-428 and KM-H2 cells was stimulated by CD40 engagement and also by coculturing L-1236 cells on primary stromal fibroblasts from HL-involved lymph nodes (HLF). Coculture experiments indicated that a direct contact of H-RS cells induces HLF cells to produce CCL5. Supernatants from L-1236, L-428 and KM-H2 cells stimulated migration of purified CD4+ T-cells and eosinophils in vitro. The migratory response to HL-cell lines supernatants was only partially neutralized (CD4+ cells: 70%; esinophils: 36%) by anti-CCL5 antibodies, reinforcing the notion that multiple chemokines are involved in the recruitment of nonmalignant reactive cells in HL tissues. Taken together, our results indicate a possible involvement of the CCR5/CCR5-ligands signaling in the regulation of H-RS cells growth and in the formation/maintenance of the typical tissue microenvironment of HL. (C) 2007 Wiley-Liss, Inc.