Qiu Yusheng, Zhu Jie, Bandi Venkata, Atmar Robert L, Hattotuwa Keith, Guntupalli Kay K, Jeffery Peter K
Lung Pathology, Department of Gene Therapy, Imperial College, Royal Brompton Hospital, London, United Kingdom.
Am J Respir Crit Care Med. 2003 Oct 15;168(8):968-75. doi: 10.1164/rccm.200208-794OC. Epub 2003 Jul 11.
We have applied immunohistology and in situ hybridization to bronchial biopsies of patients with chronic obstructive pulmonary disease (COPD) to examine neutrophil recruitment and to determine neutrophil chemoattractant and CXC receptor (CXCR) 1 and CXCR2 gene expression associated with acute severe exacerbations. Cells were counted in endobronchial biopsies of (1) patients with COPD intubated for exacerbations (E-COPD; n = 15), (2) those with COPD in a stable phase of their disease (S-COPD; n = 7), and (3) nonsmoker surgical control subjects intubated for a nonrespiratory surgical procedure (n = 15). In comparison with the nonrespiratory surgical procedure and S-COPD groups, neutrophilia and gene expression for epithelial-derived neutrophil attractant-78 (CXCL5), interleukin-8 (CXCL8), CXCR1, and CXCR2 were each upregulated in the E-COPD group (p < 0.01); compared with the S-COPD group, by 97-, 6-, 6-, 3-, and 7-fold, respectively (p < 0.01). In E-COPD, there was a significant positive association between the number of neutrophils and CXCR2 mRNA-positive cells (r = 0.79; p < 0.01) but not between the number of neutrophils and CXCR1 mRNA-positive cells. At the time of sampling of the mucosa, there was no association between neutrophil number and either the length of intubation or viral infection. Thus, in COPD, in addition to CXCL8 and CXCR1, CXCL5 and CXCR2 appear to play important roles in the airway neutrophilia characteristic of severe exacerbations.
我们运用免疫组织学和原位杂交技术，对慢性阻塞性肺疾病（COPD）患者的支气管活检样本进行检测，以研究中性粒细胞的募集情况，并确定与急性重度加重期相关的中性粒细胞趋化因子及CXC受体（CXCR）1和CXCR2基因的表达。对以下三组患者的支气管内活检样本中的细胞进行计数：（1）因病情加重而插管的COPD患者（加重期COPD；n = 15）；（2）处于疾病稳定期的COPD患者（稳定期COPD；n = 7）；（3）因非呼吸道外科手术而插管的非吸烟手术对照受试者（n = 15）。与非呼吸道外科手术组和稳定期COPD组相比，加重期COPD组的中性粒细胞增多以及上皮源性中性粒细胞趋化因子-78（CXCL5）、白细胞介素-8（CXCL8）、CXCR1和CXCR2的基因表达均上调（p < 0.01）；与稳定期COPD组相比，分别上调了97倍、6倍、6倍、3倍和7倍（p < 0.01）。在加重期COPD中，中性粒细胞数量与CXCR2 mRNA阳性细胞数量之间存在显著正相关（r = 0.79；p < 0.01），但中性粒细胞数量与CXCR1 mRNA阳性细胞数量之间无相关性。在黏膜采样时，中性粒细胞数量与插管时间或病毒感染均无关联。因此，在COPD中，除CXCL8和CXCR1外，CXCL5和CXCR2似乎在重度加重期特有的气道中性粒细胞增多中发挥重要作用。
