Impact of HIV infection on α1-antitrypsin in the lung

Sarah E. Stephenson, Carole L. Wilson, Kristina Crothers, Engi F. Attia, Cherry Wongtrakool, Irina Petrache, Lynn M. Schnapp

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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 α1-antitrypsin (A1AT), a key elastase inhibitor in the lung. Reduced levels of circulating A1AT in HIV+ patients suggest 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 HIV+ and HIV- patients with and without emphysema. 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. Total A1AT was increased in the BALF, but not in the plasma, of HIV+ compared with HIV- patients, regardless of the presence or absence of emphysema. However, antielastase activity was decreased in BALF from HIV+ patients, suggesting impaired A1AT function. Higher levels of the oxidized form of A1AT were detected in BALF from HIV+ than HIV- patients, which may account for the decreased antielastase activity. 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.

Original languageEnglish (US)
Pages (from-to)L583-L592
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume314
Issue number4
DOIs
StatePublished - Apr 1 2018
Externally publishedYes

Fingerprint

HIV Infections
HIV
Lung
Emphysema
Bronchoalveolar Lavage Fluid
Pancreatic Elastase
Age Distribution
Post Translational Protein Processing
Polymerization
Lung Diseases
Thorax
Western Blotting
Enzyme-Linked Immunosorbent Assay

Keywords

  • Emphysema
  • HIV
  • α-antitrypsin

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Cite this

Stephenson, S. E., Wilson, C. L., Crothers, K., Attia, E. F., Wongtrakool, C., Petrache, I., & Schnapp, L. M. (2018). Impact of HIV infection on α1-antitrypsin in the lung. American Journal of Physiology - Lung Cellular and Molecular Physiology, 314(4), L583-L592. https://doi.org/10.1152/ajplung.00214.2017

Impact of HIV infection on α1-antitrypsin in the lung. / Stephenson, Sarah E.; Wilson, Carole L.; Crothers, Kristina; Attia, Engi F.; Wongtrakool, Cherry; Petrache, Irina; Schnapp, Lynn M.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 314, No. 4, 01.04.2018, p. L583-L592.

Research output: Contribution to journalArticle

Stephenson, SE, Wilson, CL, Crothers, K, Attia, EF, Wongtrakool, C, Petrache, I & Schnapp, LM 2018, 'Impact of HIV infection on α1-antitrypsin in the lung', American Journal of Physiology - Lung Cellular and Molecular Physiology, vol. 314, no. 4, pp. L583-L592. https://doi.org/10.1152/ajplung.00214.2017
Stephenson, Sarah E. ; Wilson, Carole L. ; Crothers, Kristina ; Attia, Engi F. ; Wongtrakool, Cherry ; Petrache, Irina ; Schnapp, Lynn M. / Impact of HIV infection on α1-antitrypsin in the lung. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2018 ; Vol. 314, No. 4. pp. L583-L592.
@article{d533b6b035ca46e2bbf46e97c0df7949,
title = "Impact of HIV infection on α1-antitrypsin in the lung",
abstract = "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 α1-antitrypsin (A1AT), a key elastase inhibitor in the lung. Reduced levels of circulating A1AT in HIV+ patients suggest 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 HIV+ and HIV- patients with and without emphysema. 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. Total A1AT was increased in the BALF, but not in the plasma, of HIV+ compared with HIV- patients, regardless of the presence or absence of emphysema. However, antielastase activity was decreased in BALF from HIV+ patients, suggesting impaired A1AT function. Higher levels of the oxidized form of A1AT were detected in BALF from HIV+ than HIV- patients, which may account for the decreased antielastase activity. 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.",
keywords = "Emphysema, HIV, α-antitrypsin",
author = "Stephenson, {Sarah E.} and Wilson, {Carole L.} and Kristina Crothers and Attia, {Engi F.} and Cherry Wongtrakool and Irina Petrache and Schnapp, {Lynn M.}",
year = "2018",
month = "4",
day = "1",
doi = "10.1152/ajplung.00214.2017",
language = "English (US)",
volume = "314",
pages = "L583--L592",
journal = "American Journal of Physiology",
issn = "1040-0605",
publisher = "American Physiological Society",
number = "4",

}

TY - JOUR

T1 - Impact of HIV infection on α1-antitrypsin in the lung

AU - Stephenson, Sarah E.

AU - Wilson, Carole L.

AU - Crothers, Kristina

AU - Attia, Engi F.

AU - Wongtrakool, Cherry

AU - Petrache, Irina

AU - Schnapp, Lynn M.

PY - 2018/4/1

Y1 - 2018/4/1

N2 - 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 α1-antitrypsin (A1AT), a key elastase inhibitor in the lung. Reduced levels of circulating A1AT in HIV+ patients suggest 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 HIV+ and HIV- patients with and without emphysema. 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. Total A1AT was increased in the BALF, but not in the plasma, of HIV+ compared with HIV- patients, regardless of the presence or absence of emphysema. However, antielastase activity was decreased in BALF from HIV+ patients, suggesting impaired A1AT function. Higher levels of the oxidized form of A1AT were detected in BALF from HIV+ than HIV- patients, which may account for the decreased antielastase activity. 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.

AB - 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 α1-antitrypsin (A1AT), a key elastase inhibitor in the lung. Reduced levels of circulating A1AT in HIV+ patients suggest 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 HIV+ and HIV- patients with and without emphysema. 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. Total A1AT was increased in the BALF, but not in the plasma, of HIV+ compared with HIV- patients, regardless of the presence or absence of emphysema. However, antielastase activity was decreased in BALF from HIV+ patients, suggesting impaired A1AT function. Higher levels of the oxidized form of A1AT were detected in BALF from HIV+ than HIV- patients, which may account for the decreased antielastase activity. 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.

KW - Emphysema

KW - HIV

KW - α-antitrypsin

UR - http://www.scopus.com/inward/record.url?scp=85045530671&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85045530671&partnerID=8YFLogxK

U2 - 10.1152/ajplung.00214.2017

DO - 10.1152/ajplung.00214.2017

M3 - Article

VL - 314

SP - L583-L592

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 1040-0605

IS - 4

ER -