Impact of HIV Infection on Alpha-1 Antitrypsin in the Lung.

Impact of HIV Infection on Alpha-1 Antitrypsin in the Lung.

Am J Physiol Lung Cell Mol Physiol. 2017 Dec 14;:

Authors: Stephenson SE, Wilson CL, Crothers K, Attia EF, Wongtrakool C, Petrache I, Schnapp LM

Abstract
BACKGROUND: Emphysema is one of the most common lung diseases in HIV+ individuals. The pathogenesis of HIV-associated emphysema remains unclear; however, radiographic distribution and earlier age of presentation of emphysema in the lungs of HIV+ patients are similar to deficiency of alpha-1 antitrypsin (A1AT), a key elastase inhibitor in the lung. Reduced levels of circulating A1AT have been detected in HIV+ patients, suggesting a potential mechanism for emphysema development. In the present study, we asked if A1AT levels and activity in the bronchoalveolar lavage fluid (BALF) differ in patients with and without HIV and emphysema.
METHODS: A1AT levels were measured by ELISA in plasma and BALF from a cohort of 21 HIV+ and 29 HIV- patients with or without emphysematous changes on chest CT scan. To analyze A1AT function, we measured elastase activity in the BALF and assessed oxidation and polymerization of A1AT by western blotting.
RESULTS: Total A1AT was increased in the BALF but not in the plasma of HIV+ compared to HIV- patients, regardless of the presence or absence of emphysema. However, there was decreased anti-elastase activity in BALF from HIV+ patients, suggesting impaired A1AT function. Higher levels of the oxidized form of A1AT were detected in HIV+ BALF as compared to HIV-, which may account for the decreased anti-elastase activity.
CONCLUSION: These findings suggest that in the lungs of HIV+ patients, posttranslational modifications of A1AT produce a "functional deficiency" of this critical elastase inhibitor, which may contribute to emphysema development.

PMID: 29351445 [PubMed - as supplied by publisher]

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2DmurZV
via IFTTT