Expression of the neutrophil-activating CXC chemokine ENA-78/CXCL5 by human eosinophils
Expression of the neutrophil-activating CXC chemokine ENA-78/CXCL5 by human eosinophils
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DOI：
10.1046/j.1365-2222.2003.01609.x
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发表时间：
2003-04-01
影响因子：
6.1
通讯作者：
Egesten, A
中科院分区：
文献类型：
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作者：
Persson, T;Monsef, N;Egesten, A
研究背景嗜酸性粒细胞在蠕虫感染、哮喘、溃疡性结肠炎和某些肿瘤性疾病的炎症部位可见。它们也与结缔组织重塑有关，例如在长期哮喘中。在本研究中，我们研究了嗜酸性粒细胞是否表达CXC趋化因子上皮细胞衍生的中性粒细胞激活肽，ENA-78/CXCL 5是一种能激活中性粒细胞并具有血管生成特性的趋化因子，免疫细胞化学检测到嗜酸性粒细胞中的CXCL 5，免疫电镜观察到CXCL 5定位于嗜酸性粒细胞的特异性颗粒中。通过酶联免疫吸附测定（ELISA）检测到每10（6）个细胞12 +/- 2 pg（平均值+/- SEM）的CXCL 5。通过RT-PCR可以在新鲜分离的嗜酸性粒细胞中检测到CXCL 5以及相关的CXC趋化因子IL-8/CXCL 8的弱组成性表达。然而，在嗜酸性粒细胞的长时间孵育期间，如通过RT-PCR检测到的，观察到CXCL 5和IL-8/CXCL 8表达的强烈增加，并且通过ELISA在孵育培养基中检测到CXCL 5肽的量随时间增加。在长时间孵育期间添加TNF-α中和抗体显著抑制CXCL 5的产生，表明嗜酸性粒细胞自身产生的TNF-α的自分泌和旁分泌效应的参与。结论嗜酸性粒细胞通过表达CXCL 5，可以募集并激活炎症部位的中性粒细胞等携带CXC受体2（CXCR 2）的细胞。嗜酸性粒细胞也可以通过释放这种肽来促进结缔组织重塑。
Background Eosinophils are seen at sites of inflammation in diseases such as helminthic infestation, asthma, ulcerative colitis and some neoplastic diseases. They are also associated with connective tissue remodelling, for example in longstanding asthma. In the present study, we investigated whether eosinophils express the CXC chemokine epithelial cell-derived neutrophil activating peptide (ENA-78/CXCL5), a chemokine that can activate neutrophils and in addition possesses angiogenic properties.Immunocytochemistry detected CXCL5 in eosinophils and the peptide was localized in the specific granules by immunoelectron microscopy.Methods and Results In eosinophil lysates, 12 +/- 2 pg (mean +/- SEM) of CXCL5 was detected per 10(6) cells by enzyme-linked immunosorbent assay (ELISA). Weak constitutive expression of CXCL5, as well as the related CXC chemokine IL-8/CXCL8, could be detected in freshly isolated eosinophils by RT-PCR. However, during prolonged incubation of eosinophils, a strong increase in both CXCL5 and IL-8/CXCL8 expression was seen, as detected by RT-PCR, and increasing amounts of CXCL5 peptide with time were detected in the incubation medium by ELISA. Addition of TNF-alpha neutralizing antibodies during prolonged incubation significantly inhibited CXCL5 production, demonstrating involvement of auto- and paracrine effects from TNF-alpha produced by eosinophils themselves. Addition of IFN-gamma showed a strong inhibitory effect on CXCL5 synthesis.Conclusion These findings suggest that, through expression of CXCL5, eosinophils can recruit and activate CXC receptor 2 (CXCR2)-bearing cells such as neutrophils at sites of inflammation. Eosinophils may also promote connective tissue remodelling through release of this peptide.