title: Biopsy neutrophilia, neutrophil chemokine and receptor gene expression in severe exacerbations of chronic obstructive pulmonary disease.
abstract: 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.
authors.affiliation: Lung Pathology, Department of Gene Therapy, Imperial College, Royal Brompton Hospital, London, United Kingdom.
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Qiu
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.forename: Venkata
authors.initials: V
authors.lastname: Bandi
authors.forename: Robert L
authors.initials: RL
authors.lastname: Atmar
authors.forename: Keith
authors.initials: K
authors.lastname: Hattotuwa
authors.forename: Kay K
authors.initials: KK
authors.lastname: Guntupalli
authors.forename: Peter K
authors.initials: PK
authors.lastname: Jeffery
mesh_terms: D000208:Acute Disease; D000368:Aged; D001706:Biopsy; D001999:Bronchoscopy; D016022:Case-Control Studies; D054365:Chemokine CXCL5; D019743:Chemokines, CXC; D005260:Female; D005541:Forced Expiratory Volume; D015870:Gene Expression / Q000235:genetics / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007249:Inflammation; D016209:Interleukin-8 / Q000031:analogs & derivatives* / Q000032:analysis / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020556:Neutrophil Infiltration / Q000276:immunology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology* / Q000473:pathology*; D023062:Receptors, Interleukin-8A / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D023063:Receptors, Interleukin-8B / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D020545:Respiratory Mucosa / Q000276:immunology / Q000473:pathology; D012720:Severity of Illness Index; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
chemical_list: C486263:CXCL5 protein, human; D054365:Chemokine CXCL5; D019743:Chemokines, CXC; D016209:Interleukin-8; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B