Differential expression of CCR3 and CXCR3 by human lung and bone marrow-derived mast cells: implications for tissue mast cell migration
Differential expression of CCR3 and CXCR3 by human lung and bone marrow-derived mast cells: implications for tissue mast cell migration
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DOI：
10.1189/jlb.0904511
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发表时间：
2005-05-01
影响因子：
5.5
通讯作者：
Bradding, P
中科院分区：
文献类型：
--
作者：
Brightling, CE;Kaur, D;Bradding, P
在哮喘中，肥大细胞在特定的呼吸道结构中的选择性微定位在炎症性肺疾病的病理生理学中是重要的。趋化因子可能是促使肥大细胞迁移到这些组织间的候选因素。在这项研究中，我们确定了人肺肥大细胞(HLMC)与人骨髓肥大细胞(BM)和人肥大细胞系HMC-1的趋化因子受体图谱。CXC趋化因子受体3(CXCR3)是体外培养的HLMC中表达最高的趋化因子受体，免疫组织化学检测证实CXCR3在支气管粘膜肥大细胞中有表达。CXCR3具有功能，通过CXCL9、-10和-11诱导胞浆内游离钙离子、肌动蛋白重组和趋化作用的增加。CXCR3的激活不能诱导脱颗粒或细胞因子的合成。此外，超过10%的体外HLMC表达CC趋化因子受体3、CXCR1和CXCR4。有趣的是，CXCR3在人骨髓来源的肥大细胞中不表达，这表明它的表达是在组织成熟过程中诱导的。由于CXCR3配体在许多肺部疾病中升高，CXCR3可能对确定人肺内肥大细胞的解剖微定位很重要。
The selective microlocalization of mast cells within specific airway structures, such as the airway smooth muscle and submucosal glands, in asthma is important in the pathophysiology of inflammatory lung disease. Chemokines are likely candidates niediating mast cell migration into these tissue compartments. In this study, we have defined the chemokine receptor profile of human lung mast cells (HLMC) compared with mast cells derived from human bone marrow (BM) and the human mast cell line HMC-1. CXC chemokine receptor 3 (CXCR3) was the most highly expressed chemokine receptor oil ex vivo HLMC analyzed by flow cytometry, and CXCR3 expression by mast cells in the bronchial mucosa was confirmed by immuno-histochemistry. CXCR3 was functional, inducing a rise in cytosolic-free Ca2+, actin reorganization, and chemotaxis in response to the CXC ligands CXCL9, -10, and -11. CXCR3 activation did not induce degranulation or cytokine synthesis. In addition, more than 10% of ex vivo HLMC expressed CC chemokine receptor 3, CXCR1, and CXCR4. It is interesting that CXCR3 was not expressed by human BM-derived mast cells, suggesting its expression is induced during tissue maturation. As CXCR3 ligands are elevated in many pulmonary diseases, CXCR3 may be important for determining the anatomical microlocalization of mast cells within the human lung.