RT Journal Article
SR Electronic
T1 ADAM9 is upregulated in human COPD lungs and in human and murine lung in response to cigarette smoke
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 4856
VO 44
IS Suppl 58
A1 Francesca Polverino
A1 Maria Laucho Contreras
A1 Miguel Divo
A1 Victor Pinto-Plata
A1 Bartolome Celli
A1 Caroline Ann Owen
YR 2014
UL http://erj.ersjournals.com/content/44/Suppl_58/4856.abstract
AB Background: ADAM9 (A9) is a member of the family of proteinases with a disintegrin and a metalloproteinase domain. It is known to be expressed by cells germane to the pathogenesis of COPD, but it is not clear whether it contributes to COPD pathogenesis. Our goal was to begin to address this knowledge gap.Methods: Immunostaining was used to quantify A9 expression in alveolar macrophages (AMs), and alveolar and bronchial epithelial cells in lung sections from 11 smokers with COPD (GOLD I-IV); 5 control smokers (SC), and 5 non-smokers (NSC) undergoing surgery for pulmonary nodules or LVRS. A9 mRNA levels were also quantified using qPCR in lungs from WT mice exposed to air or CS for one month.Results: COPD patients had higher A9 expression in AMs (Median, Range: 51.5; 19.1-197 Fl Units/pixel2) when compared to SC (19, 9-168) and NSC (13, 5-31). COPD patients also had higher A9 expression in alveolar (41;16-725) and bronchial (51, 105-31.5) epithelial cells compared with SC (21.5, 9-189; 26, 14-76) and NSC (15, 6-140; 14, 6-26, respectively). Moreover, SC had higher A9 expression compared to NSC (p < 0.001 for all comparisons). Within the COPD group, the expression of A9 in AMs was increased in patients with COPD GOLD III-IV (55, 32-196) vs. GOLD I-II (40.5, 19-122) (p < 0.001). A9 upregulation in response to CS was confirmed in an animal model as CS-exposed C57BL/6 WT mice had 2-fold higher A9 mRNA levels than air-exposed animals.Conclusions: ADAM9 expression is increased in alveolar macrophages and lung epithelial cells in COPD patients. A9 is also upregulated in lungs of CS-exposed mice. Thus, ADAM9 may have potential to contribute to COPD pathogenesis.