ADAM17 and related epithelial injury markers in bronchoalveolar lavage and blood distinguish COPD from controls.

BACKGROUND

Chronic obstructive pulmonary disease (COPD) has many known dysregulated inflammatory proteins. A disintegrin and metalloproteinase 17 (ADAM17) is a protease that sheds several proteins involved in COPD pathogenesis. The aim was to investigate ADAM17, its phosphorylated form (pADAM17) and its substrates in bronchoalveolar lavage (BAL) and blood from COPD and control subjects.

METHODS

Groups were matched by sex, age, BMI and smoking status to compare between COPD, smoking and never smoking control subjects. The expression of ADAM17 and pADAM17 was assessed using immunofluorescence in BAL cells (n = 6-13). Concentrations of soluble ADAM17 and its substrates were quantified using ELISA or Luminex in BAL fluid (BALF, n = 11-14) and blood (n = 10-30).

RESULTS

COPD BAL samples had more ADAM17+ and pADAM17+ cells than controls and intracellular localisations were observed in epithelial cells of subjects with a smoking history. These elevations coincided with higher concentrations of several of the ADAM17 substrates in BALF from Smokers and COPD subjects, most prominently was the increased BALF HB-EGF found in COPD but not Smokers. Other changes in blood were also mostly related to epithelial injury and repair.

CONCLUSIONS

Our findings highlight an overabundance of ADAM17 and pADAM17 in COPD airways that is accentuated beyond smoking-induced changes. This broad catalytic-complex analysis has both combined individual biomarkers and discovered more novel disease-specific biomarkers that may all relate to the overarching functionality of ADAM17 in COPD, warranting further investigation into the role this enzyme plays in COPD pathogenesis.