Role of CD13 (aminopeptidase-N) in the regulation of TNF-alpha induced neutrophil apoptosis

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Neutrophils are special cells that circulate in the blood and play a major role in helping the body fight infection. They are highly motile and migrate to areas of infection, where they destroy bacteria. Thereafter, these cells are designed to die by a process called apoptosis, which triggers their safe removal. Failure of apoptosis results in the cells remaining within the inflamed site where they cause inadvertent damage to normal tissues. This is a particular problem in patients with inflammatory lung, kidney and joint disease, where persistence of the neutrophils drives chronic inflammation and organ damage. This project will look at how a molecule on the surface of neutrophils called CD13 can influence the ability of neutrophils to undergo apoptosis, especially at the inflamed site. The lab has shown a natural variation in the expression of CD13 between people, which affects the sensitivity of neutrophils to undergo apoptosis and that chemical inhibitors of CD13 may restore neutrophil apoptosis. These drugs may therefore have the potential to treat chronic inflammation. The project will utilize cell biology techniques using neutrophils from human blood, mice deficient in CD13 and inflammatory neutrophils derived from experimental subjects.