Monocytes and macrophages in alpha-1 antitrypsin deficiency

Kylie B. R. Belchamber, Eloise M. Walker, Robert A. Stockley, Elizabeth Sapey

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Abstract

Alpha-1 antitrypsin deficiency (AATD) is a genetic condition characterised by low circulating levels of alpha-1 antitrypsin (AAT), a serine proteinase inhibitor. The most common deficiency variants are the S and Z mutations, which cause the accumulation of misfolded AAT in hepatocytes resulting in endoplasmic reticular stress and insufficient release of AAT into the circulation (<11μmol/L). This leads to liver disease, as well as an increased risk of emphysema due to unopposed proteolytic activity of neutrophil-derived serine proteinases in the lungs. AATD has been traditionally viewed as an inflammatory disorder caused directly by a proteinase-antiproteinase imbalance in the lung, but increasing evidence suggests that low AAT levels may affect other cellular functions. Recently, AAT polymers have been identified in both monocytes and macrophages from AATD patients and evidence is building that these cells may also play a role in the development of AATD lung disease. Alveolar macrophages are phagocytic cells that are important in the lung immune response but are also implicated in driving inflammation. This review explores the potential implications of monocyte and macrophage involvement in non-liver AAT synthesis and the pathophysiology of AATD lung disease.

Original languageEnglish
Pages (from-to)3183-3192
Number of pages10
JournalInternational Journal of COPD
Volume15
DOIs
Publication statusPublished - 3 Dec 2020

Keywords

  • Alpha-1 antitrypsin
  • Alpha-1 antitrypsin deficiency
  • Macrophage
  • Monocyte

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Health Policy
  • Public Health, Environmental and Occupational Health

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