Monocyte-like and mature macrophages produce CXCL13 (B cell-attracting chemokine 1) in inflammatory lesions with lymphoid neogenesis
Monocyte-like and mature macrophages produce CXCL13 (B cell-attracting chemokine 1) in inflammatory lesions with lymphoid neogenesis
复制标题
DOI：
10.1182/blood-2004-02-0701
复制
发表时间：
2004-11-15
期刊：
影响因子：
20.3
通讯作者：
Brandtzaeg, P
中科院分区：
文献类型：
--
作者：
Carlsen, HS;Baekkevold, ES;Brandtzaeg, P
稳态趋化因子CXCL 13（也称为B细胞吸引趋化因子1 [BCA-1]或B淋巴细胞趋化因子[BLC]）在次级淋巴结组织中组成型表达，当在小鼠中异常表达时启动淋巴结新生。在与人类淋巴新生相关的慢性炎症中也检测到CXCL 13，表明其具有致病作用。滤泡树突状细胞（Follicular dendritic cells，FDCs）通常被认为是正常和异常淋巴组织中CXCL 13的主要来源。相反，我们发现类风湿性关节炎和溃疡性结肠炎中大多数表达CXCL 13的细胞是单核细胞/巨噬细胞系。它们位于FDC网络内的不规则淋巴结聚集体中，但也位于未检测到FDC的病变组织中较小的B细胞集合内或附近。这些表达CXCL 13的细胞中有一些是CD 14（+），表明来源于最近外渗的单核细胞。有趣的是，在体外用脂多糖刺激的来自健康供体的单核细胞分泌CXCL 13。这种诱导的产生在单核细胞向巨噬细胞体外成熟后增强，但在向树突状细胞成熟后显著降低。总之，我们的研究结果强烈表明，新招募的单核细胞/巨噬细胞在人类炎症性疾病中的淋巴新生中发挥作用。因此，循环单核细胞是未来慢性炎症靶向治疗的潜在候选者。(C)2004年，美国血液学会。
The homeostatic chemokine CXCL13 (also called B cell-attracting chemokine 1 [BCA-1] or B-lymphocyte chemoattractant [BLC]) is constitutively expressed in secondary lymphold tissue and initiates lymphold neogenesis when expressed aberrantly in mice. CXCL13 has also been detected in chronic inflammation associated with human lymphoid neogenesis, suggesting a pathogenic role. Follicular dendritic cells (FDCs) are generally considered to be the major source of CXCL13 both in normal and aberrant lymphoid tissue. We show here, instead, that most CXCL13-expressing cells in rheumatoid arthritis and ulcerative colitis are of monocyte/macrophage lineage. They are located in irregular lymphold aggregates within an FDC network, but also within and near smaller collections of B cells in diseased tissue where no FDCs are detected. Some of these CXCL13-expressing cells are CD14(+), suggesting derivation from recently extravasated monocytes. Interestingly, monocytes from healthy donors stimulated in vitro with lipopolysaccharide secrete CXCL13. This induced production is enhanced after in vitro maturation of the monocytes toward macrophages but markedly decreased after maturation toward dendritic cells. Together, our findings strongly suggest that newly recruited monocytes/macrophages play a role for lymphoid neogenesis in human inflammatory diseases. Circulating monocytes are therefore potential candidates for future targeted therapy of chronic inflammation. (C) 2004 by The American Society of Hematology.