Katoh Shigeki, Fukushima Kiyoyasu, Matsumoto Nobuhiro, Ehara Naomi, Matsumoto Kiyoshi, Yamauchi Akira, Hirashima Mitsuomi
Department of Cell Regulation, School of Medicine, Kagawa University, Kita-gun, Kagawa, Japan.
Int Arch Allergy Immunol. 2005 Jul;137(3):229-35. doi: 10.1159/000086335. Epub 2005 Jun 13.
Since human peripheral eosinophils have been shown to migrate to the CXC chemokine receptor 3 (CXCR3) ligands IFN-gamma-inducible protein 10 (IP10) and monokine induced by IFN-gamma (Mig), this confirms that CXCR3 is functionally expressed on these cells. IP10 expression has been shown to be increased in the airways of asthmatics. Eosinophil accumulations are found in bronchoalveolar lavage fluid (BALF) from patients with chronic eosinophilic pneumonia (CEP). To examine the contribution of IP10 and Mig in the pathogenesis of CEP, we measured the concentration of IP10 and Mig, and evaluated the expression of CXCR3 on eosinophils in BALF taken from patients with CEP.
The concentrations of IP10 and Mig in BALF were measured by ELISA. The proportion of CXCR3-expressing CD4+ T cells and CD16-negative eosinophils was determined by flow cytometry.
The BALF concentrations of IP10 and Mig were higher in patients with CEP, as well as in patients with sarcoidosis, when compared to healthy controls. The absolute number of CXCR3+ CD4+ T cells was significantly higher in the BALF of patients with sarcoidosis, but not in the patients with CEP, when compared to healthy volunteers. There were higher percentages of CXCR3-expressing eosinophils in the BALF than in the peripheral blood of patients with CEP.
Our findings suggest that IP10 and Mig contribute to the accumulation of CXCR3-expressing eosinophils in the lungs of patients with CEP, and modulate the eosinophilic inflammation of the lung.
由于已证明人类外周嗜酸性粒细胞可迁移至CXC趋化因子受体3(CXCR3)配体γ干扰素诱导蛋白10(IP10)和γ干扰素诱导的单核因子(Mig),这证实CXCR3在这些细胞上有功能表达。已表明哮喘患者气道中IP10表达增加。在慢性嗜酸性粒细胞性肺炎(CEP)患者的支气管肺泡灌洗液(BALF)中发现有嗜酸性粒细胞聚集。为了研究IP10和Mig在CEP发病机制中的作用,我们测量了CEP患者BALF中IP10和Mig的浓度,并评估了嗜酸性粒细胞上CXCR3的表达。
通过酶联免疫吸附测定法(ELISA)测量BALF中IP10和Mig的浓度。通过流式细胞术确定表达CXCR3的CD4 + T细胞和CD16阴性嗜酸性粒细胞的比例。
与健康对照相比,CEP患者以及结节病患者的BALF中IP10和Mig的浓度更高。与健康志愿者相比,结节病患者BALF中CXCR3 + CD4 + T细胞的绝对数量显著更高,但CEP患者中并非如此。CEP患者BALF中表达CXCR3的嗜酸性粒细胞百分比高于外周血。
我们的研究结果表明,IP10和Mig促成了CEP患者肺部表达CXCR3的嗜酸性粒细胞的聚集,并调节了肺部的嗜酸性粒细胞炎症。