A disintegrin and metalloprotease 17 (ADAM17) is most known for the activation of pro tumor necrosis factor-?, but the functions of this sheddase extends to over 80 other cell surface proteins. ADAM17 has been linked to inflammation and fibrosis in COPD among other diseases, but its role in asthma and, the role of its substrates is less clear. Therefore, we aimed to assess the levels of 18 ADAM17 substrates in airway and blood samples of COPD, asthmatic, and healthy individuals.

Bronchoalveolar lavage fluid (BALF) and plasma were collected from COPD (BALF: n=13, plasma: n=25), asthmatics (n=8, n=25) and paired healthy subjects (n=21, n=50). The substrates were quantified in both BALF and plasma samples using the Luminex Assay. COPD and asthma were compared to their respective paired healthy controls.

We found that MHC class I polypeptide?related sequence A (MICA) levels from COPD patients was lower in the blood (p=0.0383). Mucin 1 (MUC1) in BALF from COPD patients (p=0.0500) was also lower. Interleukin 6 receptor-? (IL-6R-?) was lower in blood from COPD patients (p=0.0098) but higher in blood from asthmatics (p= 0.0563). Syndecan-1 was lower in BALF from asthmatics (p=0.0128).

Collectively the COPD findings suggest that there is an increased cell death response. Lower levels of soluble MICA might mean higher levels of membrane bound which triggers NK-cell mediated cytotoxicity. The lower MUC-1 levels might lead to a higher number of mucosal pathogen infected cells. The lower levels of Syndecan-1 and higher of IL 6R-? indicate an increase in inflammation. Conclusively ADAM17 and its substrates have an impact on the disease profile of individuals with COPD and asthma.