Lung and Allergy Research, The National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Innate Immun. 2012 Jun;18(3):503-10. doi: 10.1177/1753425911423270. Epub 2011 Oct 13.
Neutrophils are among the first cells to arrive at the site of injury. Chemokines secreted by neutrophils affect the migration of both neutrophils and other inflammatory cells, such as monocytes. It has been reported that LPS-induced release of IL-8 (CXCL-8) by neutrophils is amplified by neutrophil-derived TNF-α. We hypothesize that chemokine release by neutrophils is altered in chronic obstructive pulmonary disease (COPD) compared with healthy controls and that TNF-α may be involved in this alteration. Peripheral blood neutrophils isolated from smokers with COPD (n = 12), smokers without COPD (n = 12) and healthy, non-smokers (n = 12) were stimulated with LPS, TNF-α or organic dust. Anti-TNF-α Ab (infliximab) was used to study the effect of neutrophil-derived TNF-α. Release of CXCL-8, macrophage inflammatory protein-1 α (MIP-1α, CCL-3), monocyte chemotactic protein-1 (MCP-1, CCL-2) and TNF-α was measured. Neutrophils spontaneously released CXCL-8, CCL-2 and CCL-3. Inhibition of TNF-α reduced the spontaneous release of CXCL-8 and CCL-3. Stimulation with LPS and organic dust increased the release of CXCL-8 and CCL-3 (but not CCL-2) which was reduced by inhibition of TNF-α. In the COPD group, inhibition of TNF-α failed to inhibit the release of LPS-induced CXCL-8. The role of neutrophils as cytokine and chemokine producers was confirmed. Neutrophil-derived TNF-α contributed to the release of chemokines after stimulation with LPS and organic dust, as the response was inhibited by infliximab. In the COPD group, infliximab did not significantly inhibit the release of CXCL-8, suggesting that the role of TNF-α is altered in COPD.
中性粒细胞是最早到达损伤部位的细胞之一。中性粒细胞分泌的趋化因子影响中性粒细胞和其他炎症细胞（如单核细胞）的迁移。据报道，中性粒细胞衍生的 TNF-α 可放大 LPS 诱导的中性粒细胞释放 IL-8（CXCL-8）。我们假设与健康对照组相比，慢性阻塞性肺疾病（COPD）患者的中性粒细胞趋化因子释放发生改变，并且 TNF-α 可能参与这种改变。从 COPD 吸烟者（n=12）、无 COPD 吸烟者（n=12）和健康非吸烟者（n=12）中分离外周血中性粒细胞，用 LPS、TNF-α 或有机粉尘刺激，并用抗 TNF-α Ab（英夫利昔单抗）研究中性粒细胞衍生 TNF-α 的作用。测量 CXCL-8、巨噬细胞炎性蛋白-1α（MIP-1α，CCL-3）、单核细胞趋化蛋白-1（MCP-1，CCL-2）和 TNF-α 的释放。中性粒细胞自发释放 CXCL-8、CCL-2 和 CCL-3。TNF-α 的抑制减少了 CXCL-8 和 CCL-3 的自发释放。LPS 和有机粉尘的刺激增加了 CXCL-8 和 CCL-3 的释放（但不增加 CCL-2），而 TNF-α 的抑制减少了这种释放。在 COPD 组中，TNF-α 的抑制未能抑制 LPS 诱导的 CXCL-8 的释放。中性粒细胞作为细胞因子和趋化因子产生细胞的作用得到了证实。中性粒细胞衍生的 TNF-α 促进 LPS 和有机粉尘刺激后的趋化因子释放，因为英夫利昔单抗抑制了该反应。在 COPD 组中，英夫利昔单抗并未显著抑制 CXCL-8 的释放，表明 TNF-α 的作用在 COPD 中发生改变。
