ABSTRACT
Neutrophil accumulation at infl ammatory sites is an important component of innate immunity and is required for the host’s ability to kill invading pathogens. However, exaggerated neutrophil accumulation can also lead to unwanted tissue damages and infl ammation. Neutrophils are short-lived and die via constitutive and spontaneous apoptosis. Th is tightly regulated cellular death program plays a crucial role in neutrophil homeostasis and the resolution of infl ammation. It needs to be well controlled to provide a good balance between neutrophils’ immune functions and their safe clearance. Dysregulation of neutrophil apoptosis was implicated in a variety of infectious and infl ammatory diseases, and thus this cellular process has been considered to be a legitimate therapeutic target for the treatment of these diseases (e.g. lung infl ammation, asthma, multiple sclerosis, arthritis, gastritis and infl ammatory bowel disease). In this chapter, we summarize recent studies on the molecular basis of neutrophil spontaneous death. Th e intracellular components
leading to neutrophil apoptosis, such as caspase, calpain, cathepsin, mitochondria, reactive oxygen species (ROS), PI3K/Akt, MAPK, protein kinase C (PKC), and Bcl-2 family member proteins are discussed. A variety of extracellular stimuli that enhance or delay neutrophil apoptosis, such as cytokines, cell adhesion, phagocytosis, red blood cells, and platelets, are also summarized. Finally, we review the current understanding regarding the involvement of neutrophil apoptosis in various infectious and infl ammatory diseases.
