IL-8 and its CXCR1 and CXCR2 receptors participate in the control of megakaryocytic proliferation, differentiation, and ploidy in myeloid metaplasia with myelofibrosis
IL-8 and its CXCR1 and CXCR2 receptors participate in the control of megakaryocytic proliferation, differentiation, and ploidy in myeloid metaplasia with myelofibrosis
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DOI：
10.1182/blood-2003-12-4415
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发表时间：
2005-01-15
期刊：
影响因子：
20.3
通讯作者：
Le Bousse-Kerdilès, MC
中科院分区：
文献类型：
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作者：
Emadi, S;Clay, D;Le Bousse-Kerdilès, MC
骨髓增生、骨髓纤维化和新生血管生成是骨髓化生伴骨髓纤维化（MMM）的三个主要内在病理生理特征。骨髓增生的特征是循环CD34（+）祖细胞数量增加，脾和肝中营养不良巨核细胞（MK）细胞显著扩增和骨髓化生。白细胞介素8 （IL-8）在造血祖细胞增殖和动员以及新生血管生成中的各种生物活性促使我们分析其在MMM中的潜在作用。我们发现患者血清中IL-8趋化因子水平显著升高，包括血小板在内的多种造血细胞参与其产生。在体外，通过中和或反义抗IL-8处理抑制CD34（+）细胞表达的自分泌IL-8，可增加MMM CD34（+）衍生细胞的增殖并刺激其MK分化。此外，在MK液体培养条件下，向MMM CD34（+）细胞中加入中和性抗il -8受体（CXC趋化因子受体1 [CXCR1]或2 [CXCR2]）抗体，可增加MMM CD41(+) MK细胞的增殖和分化，恢复其多倍体化。我们的研究结果表明，IL-8及其受体参与了以MMM为特征的MK生长的改变，并为这种仍然无法治愈的疾病开辟了新的治疗前景。(C) 2005年由美国血液病学会出版。
Myeloproliferation, myelofibrosis, and neoangiogenesis are the 3 major intrinsic pathophysiologic features of myeloid metaplasia with myelofibrosis (MMM). The myeloproliferation is characterized by an increased number of circulating CD34(+) progenitors with the prominent amplification of dystrophic megakaryocytic (MK) cells and myeloid metaplasia in the spleen and liver. The various biologic activities of interleukin 8 (IL-8) in hematopoietic progenitor proliferation and mobilization as well as in neoangiogenesis prompted us to analyze its potential role in MMM. We showed that the level of IL-8 chemokine is significantly increased in the serum of patients and that various hematopoietic cells, including platelets, participate in its production. In vitro inhibition of autocrine IL-8 expressed by CD34(+) cells with either a neutralizing or an antisense anti-IL-8 treatment increases the proliferation of MMM CD34(+)-derived cells and stimulates their MK differentiation. Moreover, addition of neutralizing anti-IL-8 receptor (CXC chemokine receptor 1 [CXCR1] or 2 [CXCR2]) antibodies to MMM CD34(+) cells cultured under MK liquid culture conditions increases the proliferation and differentiation of MMM CD41(+) MK cells and restores their polyploidization. Our results suggest that IL-8 and its receptors participate in the altered MK growth that features MMM and open new therapeutic prospects for this still incurable disease. (C) 2005 by The American Society of Hematology.