Plasma Chemokine signature correlates with lung goblet cell hyperplasia in smokers with and without chronic obstructive pulmonary disease

BMC Pulmonary Medicine

Thomas J. Rogers³  Gerard J. Criner¹  Heba Durra²  Michelle Oros²  William D. Cornwell³  Victor Kim¹ 

[1] Division of Pulmonary and Critical Care Medicine, Temple University School of Medicine, 3401 North Broad Street, 785 Parkinson Pavilion, Philadelphia 19140, PA, USA;Department of Pathology, Temple University School of Medicine, Philadelphia, PA, USA;Center for Inflammation, Translational and Clinical Lung Research, Temple University School of Medicine, Philadelphia, PA, USA

关键词: Macrophage;    Neutrophil;    Chemokine;    Goblet cell hyperplasia;    Chronic obstructive pulmonary disease;    Mucin;   

Others  :  1228329
DOI  :  10.1186/s12890-015-0103-2

 received in 2015-04-17, accepted in 2015-09-17,  发布年份 2015

【 摘 要 】

Background

Chronic Obstructive Pulmonary Disease (COPD) is characterized by lung and systemic inflammation as well as airway goblet cell hyperplasia (GCH). Mucin production is activated in part by stimulation of the epidermal growth factor (EGF) receptor pathway through neutrophils and macrophages. How circulating cytokine levels relate to GCH is not clear.

Methods

We performed phlebotomy and bronchoscopy on 25 subjects (six nonsmokers, 11 healthy smokers, and eight COPD subjects FEV ₁30–60 %). Six endobronchial biopsies per subject were performed. GCH was measured by measuring mucin volume density (MVD) using stereological techniques on periodic acid fast-Schiff stained samples. We measured the levels of chemokines CXCL8/IL-8, CCL2/MCP-1, CCL7/MCP-3, CCL22/MCD, CCL3/MIP-1α, and CCL4/MIP-1β, and the cytokines IL-1, IL-4, IL-6, IL-9, IL-17, EGF, and vascular endothelial growth factor (VEGF). Differences between groups were assessed using one-way ANOVA, t test, or Chi squared test. Post hoc tests after ANOVA were performed using Bonferroni correction.

Results

MVD was highest in healthy smokers (27.78 ± 10.24 μL/mm ² ) compared to COPD subjects (16.82 ± 16.29 μL/mm ² , p = 0.216) and nonsmokers (3.42 ± 3.07 μL/mm ² , p <0.0001). Plasma CXCL8 was highest in healthy smokers (11.05 ± 8.92 pg/mL) compared to nonsmokers (1.20 ± 21.92 pg/mL, p = 0.047) and COPD subjects (6.01 ± 5.90 pg/mL, p = 0.366). CCL22 and CCL4 followed the same trends. There were no significant differences in the other cytokines measured. When the subjects were divided into current smokers (healthy smokers and COPD current smokers) and non/ex-smokers (nonsmokers and COPD ex-smokers), plasma CXCL8, CCL22, CCL4, and MVD were greater in current smokers. No differences in other cytokines were seen. Plasma CXCL8 moderately correlated with MVD (r = 0.552, p = 0.003).

Discussion

In this small cohort, circulating levels of the chemokines CXCL8, CCL4, and CCL22, as well as MVD, attain the highest levels in healthy smokers compared to nonsmokers and COPD subjects. These findings seem to be driven by current smoking and are independent of airflow obstruction.

Conclusions

These data suggest that smoking upregulates a systemic pattern of neutrophil and macrophage chemoattractant expression, and this correlates significantly with the development of goblet cell hyperplasia.

【 授权许可】

   
2015 Kim et al.

【 图 表 】

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