Department of Critical Care Medicine and Pulmonary Services, Evaggelismos General Hospital, Athens, Greece.
Am J Respir Crit Care Med. 2013 Jun 1;187(11):1194-202. doi: 10.1164/rccm.201208-1543OC.
Little is known about what drives the appearance of lymphoid follicles (LFs), which may function as lymphoid organs in chronic obstructive pulmonary disease (COPD). In animal infection models, pulmonary LF formation requires expression of homeostatic chemokines by stromal cells and dendritic cells, partly via lymphotoxin.
To study the role of homeostatic chemokines in LF formation in COPD and to identify mechanism(s) responsible for their production.
Peripheral lung homeostatic chemokine and lymphotoxin expression were visualized by immunostainings and quantified by ELISA/quantitative reverse transcriptase-polymerase chain reaction in patients with COPD with and without LFs. Expression of lymphotoxin and homeostatic chemokine receptors was investigated by flow cytometry. Primary lung cell cultures, followed by ELISA/quantitative reverse transcriptase-polymerase chain reaction/flow cytometry, were performed to identify mechanisms of chemokine expression. Polycarbonate membrane filters were used to assess primary lung cell migration toward lung homogenates.
LFs expressed the homeostatic chemokine CXCL13. Total CXCL13 levels correlated with LF density. Lung B cells of patients with COPD were important sources of CXCL13 and lymphotoxin and also expressed their receptors. Cigarette smoke extract, H2O2, and LPS exposure up-regulated B cell-derived CXCL13. The LPS-induced increase in CXCL13 was partly mediated via lymphotoxin. Notably, CXCL13 was required for efficient lung B-cell migration toward COPD lung homogenates and induced lung B cells to up-regulate lymphotoxin, which further promoted CXCL13 production, establishing a positive feedback loop.
LF formation in COPD may be driven by lung B cells via a CXCL13-dependent mechanism that involves toll-like receptor and lymphotoxin receptor signaling.
关于是什么驱动了淋巴滤泡（LFs）的出现知之甚少，而 LFs 可能在慢性阻塞性肺疾病（COPD）中发挥淋巴器官的作用。在动物感染模型中，肺部 LF 的形成需要基质细胞和树突状细胞表达稳态趋化因子，部分通过淋巴毒素实现。
研究稳态趋化因子在 COPD 中 LF 形成中的作用，并确定其产生的机制。
通过免疫染色和 ELISA/定量逆转录-聚合酶链反应检测 COPD 患者肺组织中稳态趋化因子和淋巴毒素的表达，并根据是否存在 LF 进行量化。通过流式细胞术检测淋巴毒素和稳态趋化因子受体的表达。进行原代肺细胞培养，随后进行 ELISA/定量逆转录-聚合酶链反应/流式细胞术，以确定趋化因子表达的机制。使用聚碳酸酯膜过滤器评估原代肺细胞向肺组织匀浆的迁移。
LFs 表达了稳态趋化因子 CXCL13。总 CXCL13 水平与 LF 密度相关。COPD 患者的肺 B 细胞是 CXCL13 和淋巴毒素的重要来源，并且还表达了它们的受体。香烟烟雾提取物、H2O2 和 LPS 暴露上调了 B 细胞衍生的 CXCL13。LPS 诱导的 CXCL13 增加部分通过淋巴毒素介导。值得注意的是，CXCL13 是肺 B 细胞向 COPD 肺组织匀浆有效迁移所必需的，并诱导肺 B 细胞上调淋巴毒素，这进一步促进了 CXCL13 的产生，建立了一个正反馈环。
COPD 中 LF 的形成可能是由肺 B 细胞通过 CXCL13 依赖的机制驱动的，该机制涉及 Toll 样受体和淋巴毒素受体信号通路。
