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| Immune Cell Function in Alpha-1 Antitrypsin Deficiency |
| Monday, 24 November 2008 12:49 |
Immune Cell Function in Alpha-1 Antitrypsin DeficiencyAwarding Body: Talecris Biotherapeutics Project Description: Alpha-1 antitrypsin deficiency (AATD) is a hereditary disorder characterised by lung and liver manifestations. The most common form of AAT deficiency occurs due to the Z mutation, which encodes a glutamine to lysine substitution at position 342 of the AAT protein. This mutation causes the protein to fold aberrantly and accumulate in the endoplasmic reticulum (ER) of hepatocytes. The liver disease is believed to be associated with intracellular accumulation of AAT in the ER leading to ER stress responses whilst the lung disease is due to decreased levels of the AAT antiprotease in the airways, thereby facilitating proteolytic damage. In addition to hepatocytes, AAT is also expressed by other cell types including monocytes and neutrophils. We aim to demonstrate that ER accumulation of Z AAT in monocytes and neutrophils impacts on specific phenotypes and functions of these immune cells, contributing to the overall inflammatory disease process. Duration: 12 months from September 2007 |
Alpha-1 Antitrypsin is an important protein produced by the liver, which is released into the bloodstream and travels to the lungs. Once inside the lungs it provides protection from the destructive effects of infections and harmful irritants, particularly tobacco smoke.
Alpha-1 antitrypsin deficiency (Alpha-1) is a genetic condition which, along with cystic fibrosis, is the commonest genetic lung disease in Ireland. It severely affects more than 2,000 people nationally, with another 10,000 individuals also at risk of lung and liver disease. It is the only proven genetic risk factor for COPD.