A Disintegrin and Metalloproteinase Domain-9: A Novel Proteinase Culprit with Multifarious Contributions to Chronic Obstructive Pulmonary Disease

Rationale: ADAMs (proteinases with a disintegrin and a metalloproteinase domain) have not been well studied in chronic obstructive pulmonary disease (COPD).Objectives: To investigate whether ADAM9 is linked to COPD in humans and mice.Methods: ADAM9 blood and lung levels were measured in patients with COPD versus control subjects, and in air- versus cigarette smoke (CS)-exposed wild-type mice. Wild-type and Adam9−/− mice were exposed to air or CS for 1–6 months, and COPD-like lung pathologies were measured.Measurements and Main Results: ADAM9 staining was increased in lung epithelial cells and macrophages in smokers and even more so in patients with COPD and correlated directly with pack-year smoking history and inversely with airflow obstruction and/or FEV1 percent predicted. Bronchial epithelial cell ADAM9 mRNA levels were higher in patients with COPD than control subjects and correlated directly with pack-year smoking history. Plasma, BAL fluid, and sputum ADAM9 levels were similar in patients with COPD...