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

中性粒细胞是一种在血液中循环的特殊细胞，在帮助身体抵抗感染方面起着重要作用。它们的流动性很强，会迁移到感染区域，在那里消灭细菌。之后，这些细胞被设计成通过一种叫做凋亡的过程死亡，从而触发它们的安全移除。细胞凋亡的失败导致细胞留在炎症部位，对正常组织造成无意的损害。这在患有炎症性肺、肾和关节疾病的患者中是一个特别的问题，在这些疾病中，中性粒细胞的持续存在导致慢性炎症和器官损伤。该项目将研究中性粒细胞表面的CD13分子如何影响中性粒细胞进行凋亡的能力，特别是在炎症部位。该实验室已经证明了人与人之间CD13表达的自然差异，这影响了中性粒细胞对细胞凋亡的敏感性，CD13的化学抑制剂可能恢复中性粒细胞的凋亡。因此，这些药物可能具有治疗慢性炎症的潜力。该项目将利用细胞生物学技术，使用来自人类血液的中性粒细胞、缺乏CD13的小鼠和来自实验对象的炎症中性粒细胞。

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.