Monocytes and Macrophages in Alpha-1 Antitrypsin Deficiency

• Published in: International journal of chronic obstructive pulmonary disease Vol. 15; pp. 3183 - 3192
• Main Authors: Belchamber, Kylie B R, Walker, Eloise M, Stockley, Robert A, Sapey, Elizabeth
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 2020; Dove Medical Press Ltd; Dove; Dove Medical Press
• Subjects: Antigen presentation; Cytokines; Development and progression; Infections; Inflammation; Liver; Liver diseases; Lung diseases; Lungs; Macrophages; monocyte macrophage alpha-1 antitrypsin alpha-1 antitrypsin deficiency; Mutation; Neutrophils; Physiology; Polymers; Proteases; Proteins; Recruitment; Review; United Kingdom; alpha-1 antitrypsin; macrophage; monocyte; alpha-1 antitrypsin deficiency
• ISSN: 1178-2005; 1176-9106; 1178-2005
• DOI: 10.2147/COPD.S276792

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.