[Frontiers in Bioscience 14, 2372-2385, January 1, 2009]

Regulation of neutrophil apoptosis by cytokines, pathogens and environmental stressors

Julian Maggini, Silvina Raiden, Gabriela Salamone, Analia Trevani, Jorge Geffner

Institute of Hematologic Research, National Academy of Medicine, Buenos Aires, Argentina

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Regulation of neutrophil apoptosis via death receptors: the extrinsic apoptosis pathway
3.1. Fas receptors
3.2. TNF receptors
3.3. TRAIL receptors
4. Regulation of apoptosis via the mitochondria: the intrinsic apoptosis pathway
4.1. The intrinsic pathway of apoptosis in the neutrophil
4.2. Expression and function of proapoptotic proteins of the Bcl-2 familiy in the neutrophil
4.3. Expression and function of anti-apoptotic proteins of the Bcl-2 familiy in the neutrophil
5. Caspases and IAPs
6. Non-conventional pathways involved in the induction of neutrophil cell death
6.1. Induction of neutrophil cell death by ROS
6.2. Induction of neutrophil cell death by sialic binding immunoglobulin (Ig)-like lectin 9 (Siglec-9)
6.3. A novel cell death pathway that leads to neutrophil extracellular traps
7. Conclusions
8. Acknowledgments
9. References

1. ABSTRACT

As a key component of the innate immune response, neutrophils play a major role in host protection against bacterial and fungi infections. Neutrophils are short-lived phagocytic cells and, as a first line of defense against host insult, they are rapidly and massively recruited from the circulation into inflammatory sites, where the expression of their apoptotic program can be regulated by a number of agents such as cytokines, pathogens and environmental stressors. Apoptosis of neutrophils is central to homoeostasis and the resolution of inflammation. Recent studies have highlighted the complex convergence of different pathways in the regulation of neutrophil survival. This review focuses on the mechanisms involved in the induction and regulation of neutrophil apoptosis.