Hartl Dominik, Griese Matthias, Nicolai Thomas, Zissel Gernot, Prell Christine, Reinhardt Dietrich, Schendel Dolores J, Krauss-Etschmann Susanne
Childrens' Hospital, Ludwig-Maximilians-University, Munich, Germany.
Respir Res. 2005 Aug 11;6(1):93. doi: 10.1186/1465-9921-6-93.
Interstitial lung diseases (ILD) are chronic inflammatory disorders leading to pulmonary fibrosis. Monocyte chemotactic protein 1 (MCP-1) promotes collagen synthesis and deletion of the MCP-1 receptor CCR2 protects from pulmonary fibrosis in ILD mouse models. We hypothesized that pulmonary MCP-1 and CCR2+ T cells accumulate in pediatric ILD and are related to disease severity.
Bronchoalveolar lavage fluid was obtained from 25 children with ILD and 10 healthy children. Levels of pulmonary MCP-1 and Th1/Th2-associated cytokines were quantified at the protein and the mRNA levels. Pulmonary CCR2+, CCR4+, CCR3+, CCR5+ and CXCR3+ T cells were quantified by flow-cytometry.
CCR2+ T cells and MCP-1 levels were significantly elevated in children with ILD and correlated with forced vital capacity, total lung capacity and ILD disease severity scores. Children with lung fibrosis had significantly higher MCP-1 levels and CCR2+ T cells in bronchoalveolar lavage fluid compared to non-fibrotic children.
The results indicate that pulmonary CCR2+ T cells and MCP-1 contribute to the pathogenesis of pediatric ILD and might provide a novel target for therapeutic strategies.
间质性肺疾病（ILD）是导致肺纤维化的慢性炎症性疾病。单核细胞趋化蛋白1（MCP-1）促进胶原蛋白合成，在ILD小鼠模型中，MCP-1受体CCR2的缺失可预防肺纤维化。我们推测，肺部MCP-1和CCR2+ T细胞在儿童ILD中积聚，且与疾病严重程度相关。
从25例ILD患儿和10例健康儿童获取支气管肺泡灌洗液。在蛋白质和mRNA水平定量检测肺部MCP-1和Th1/Th2相关细胞因子的水平。通过流式细胞术对肺部CCR2+、CCR4+、CCR3+、CCR5+和CXCR3+ T细胞进行定量分析。
ILD患儿的CCR2+ T细胞和MCP-1水平显著升高，且与用力肺活量、肺总量和ILD疾病严重程度评分相关。与非纤维化患儿相比，肺纤维化患儿支气管肺泡灌洗液中的MCP-1水平和CCR2+ T细胞显著更高。
结果表明，肺部CCR2+ T细胞和MCP-1在儿童ILD发病机制中起作用，可能为治疗策略提供新靶点。
