Yoshikawa Takahiro, Dent Gordon, Ward Jon, Angco Gilbert, Nong Guangmin, Nomura Naho, Hirata Kazuto, Djukanovic Ratko
Allergy & Inflammation Research, Division of Infection, Inflammation, and Repair, Mailpoint 810, Level F, South Block, University of Southampton School of Medicine, Southampton General Hospital, Southampton SO16 6YD, UK.
Am J Respir Crit Care Med. 2007 Mar 1;175(5):473-9. doi: 10.1164/rccm.200507-1152OC. Epub 2006 Nov 16.
Neutrophilic airway inflammation is considered to be a major factor in the pathogenesis of chronic obstructive pulmonary disease (COPD), with sputum and bronchoalveolar lavage neutrophil counts broadly correlating with disease severity. The mechanisms responsible for neutrophil accumulation are poorly understood, but they could involve increased influx and/or survival of these cells.
To investigate whether neutrophil chemotactic responsiveness and/or chemotactic activity in airway secretions are increased in subjects with COPD.
Chemotaxis experiments were performed using induced sputum supernatants from subjects with and without COPD as a source of chemotactic activity, and neutrophils from healthy donors as responder cells. In addition, chemotactic responses to N-formyl-Met-Leu-Phe (fMLP) and interleukin-8 (IL-8/CXCL8) were studied using neutrophils from healthy subjects and subjects with COPD.
As reported in the literature, sputum neutrophil counts were significantly increased in subjects with COPD compared with healthy subjects. However, this was associated with reduced chemotactic activity in sputum in COPD, as judged by reduced chemotaxis to the fluid phase of sputum from subjects with COPD compared with healthy subjects. Furthermore, whereas neutrophils from subjects with stage I COPD had normal responses to fMLP and IL-8, subjects with more severe stage II-IV COPD showed reduced levels of spontaneous migration and chemotaxis to fMLP and IL-8.
Neither increased chemotactic activity in the airways nor increased chemotactic responsiveness of neutrophils explains the increased number of these cells in subjects with stable COPD. The implications of the observed reduction in neutrophil chemotactic activity remain to be established.
中性粒细胞气道炎症被认为是慢性阻塞性肺疾病（COPD）发病机制中的一个主要因素，痰液和支气管肺泡灌洗中的中性粒细胞计数与疾病严重程度大致相关。中性粒细胞积聚的机制尚不清楚，但可能涉及这些细胞流入增加和/或存活时间延长。
研究COPD患者气道分泌物中的中性粒细胞趋化反应性和/或趋化活性是否增加。
使用来自有或无COPD患者的诱导痰上清液作为趋化活性来源，以健康供体的中性粒细胞作为反应细胞进行趋化实验。此外，还使用健康受试者和COPD患者的中性粒细胞研究了对N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸（fMLP）和白细胞介素-8（IL-8/CXCL8）的趋化反应。
正如文献报道，与健康受试者相比，COPD患者的痰液中性粒细胞计数显著增加。然而，这与COPD患者痰液中趋化活性降低有关，与健康受试者相比，COPD患者痰液液相的趋化作用降低。此外，虽然I期COPD患者的中性粒细胞对fMLP和IL-8反应正常，但病情更严重的II-IV期COPD患者的自发迁移水平以及对fMLP和IL-8的趋化作用降低。
气道中趋化活性增加和中性粒细胞趋化反应性增加均不能解释稳定期COPD患者中这些细胞数量的增加。中性粒细胞趋化活性降低的影响尚待确定。
