Ricerc@Sapienza

Background: The deficiency of α1-antitrypsin (AAT) is secondary to misfolding and polymerization of the abnormal Z-AAT in liver cells and is associated with lung emphysema. Alveolar macrophages (AMs) produce AAT; however, it is not known whether Z-AAT can polymerize in AMs, further decreasing lung AAT and promoting lung inflammation. Our intention was to investigate whether AAT polymerizes in human AMs and to study the possible relation between polymerization and degree of lung inflammation. Methods: Immunohistochemical analysis with 2C1 monoclonal antibody specific for polymerized AAT was performed in sections of the following: nine lungs from individuals with AAT deficiency (AATD) and severe COPD; 35 smokers with normal AAT levels, of whom 24 had severe COPD and 11 did not have COPD; and 13 nonsmokers. AMs positive for AAT polymers were counted and expressed as the percentage of total AMs in the lungs. Results: AAT polymerization was detected in 27% (4%-67%) of AMs from individuals with AATD but also in AMs from smokers with normal AAT with (24% [0%-70%]) and without (24% [0%-60%]) COPD, but not in AMs from nonsmokers (0% [0%-1.5%]) (P <.0001 the="" percentage="" of="" ams="" with="" polymerized="" aat="" correlated="" pack-years="" smoked="" p=".0001)," fev1="" small="" airways="" disease="" and="" number="" cd8="" cells="" neutrophils="" in="" alveolar="" walls="" r="0.31," respectively="" conclusions:="" polymerization="" macrophages="" occurs="" lungs="" individuals="" aatd="" but="" also="" smokers="" normal="" levels="" or="" without="" copd.="" our="" findings="" highlight="" similarities="" pathophysiology="" copd="" adding="" a="" potentially="" important="" step="" to="" mechanism="">