Neutrophil Apoptosis and Its Involvement in Inflammation and Infection

Abstract

Neutrophil accumulation at inflammatory 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 inflammation. Neutrophils are short-lived and die via constitutive and spontaneous apoptosis. This tightly regulated cellular death program plays a crucial role in neutrophil homeostasis and the resolution of inflammation. It needs to be well controlled to provide a nice balance between neutrophils’ immune functions and their safe clearance. Dysregulation of neutrophil apoptosis was implicated in a variety of infectious and inflammatory diseases, and thus this cellular process has been considered to be a legitimate therapeutic target for the treatment of these diseases (e.g. lung inflammation, asthma, multiple sclerosis, arthritis, gastritis and inflammatory bowel disease). In this chapter, we summarize recent studies on the molecular basis of neutrophil spontaneous death. The intracellular components leading to neutrophil apoptosis, such as caspase, calpain, cathepsin, mitochondria, reactive oxygen species, 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 inflammatory diseases.