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 with pack-years smoked (r = 0.53, P =.0001), FEV1/FVC (r = −0.41, P =.005), small airways disease (r = 0.44, P =.004), and number of CD8+ T cells and neutrophils in alveolar walls (r = 0.51, P =.002; r = 0.31, P =.05, respectively). Conclusions: Polymerization of AAT in alveolar macrophages occurs in the lungs of individuals with AATD but also in smokers with normal AAT levels with or without COPD. Our findings highlight the similarities in the pathophysiology of COPD in individuals with and without AATD, adding a potentially important step to the mechanism of COPD.

Bazzan, E., Tine, M., Biondini, D., Benetti, R., Baraldo, S., Turato, G., et al. (2018). α1-Antitrypsin Polymerizes in Alveolar Macrophages of Smokers With and Without α1-Antitrypsin Deficiency. CHEST, 154(3), 607-616 [10.1016/j.chest.2018.04.039].

α1-Antitrypsin Polymerizes in Alveolar Macrophages of Smokers With and Without α1-Antitrypsin Deficiency

Fagiuoli S.;Sonzogni A.;
2018

Abstract

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 with pack-years smoked (r = 0.53, P =.0001), FEV1/FVC (r = −0.41, P =.005), small airways disease (r = 0.44, P =.004), and number of CD8+ T cells and neutrophils in alveolar walls (r = 0.51, P =.002; r = 0.31, P =.05, respectively). Conclusions: Polymerization of AAT in alveolar macrophages occurs in the lungs of individuals with AATD but also in smokers with normal AAT levels with or without COPD. Our findings highlight the similarities in the pathophysiology of COPD in individuals with and without AATD, adding a potentially important step to the mechanism of COPD.
Articolo in rivista - Articolo scientifico
cigarette smoking; COPD; emphysema; serpins;
English
2018
154
3
607
616
none
Bazzan, E., Tine, M., Biondini, D., Benetti, R., Baraldo, S., Turato, G., et al. (2018). α1-Antitrypsin Polymerizes in Alveolar Macrophages of Smokers With and Without α1-Antitrypsin Deficiency. CHEST, 154(3), 607-616 [10.1016/j.chest.2018.04.039].
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/354053
Citazioni
  • Scopus 17
  • ???jsp.display-item.citation.isi??? 17
Social impact