Neutrophil apoptosis pathways and their modifications in inflammation

Abstract

Neutrophils are constantly produced in large numbers in the bone marrow, and the same numbers of cells need to die within a defined time period in order to keep cellular homeostasis under physiologic conditions. Changing the rate of apoptosis rapidly changes cell numbers in such systems. For instance, in many bacterial and autoimmune inflammatory diseases, delayed apoptosis is one important mechanism for neutrophil accumulation. Excessive production of granulocyte/macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF), two important neutrophil survival factors, is often observed in such inflammatory responses. Cytokine withdrawal, as it occurs in the resolution phase of inflammation, leads to the induction of apoptosis. Moreover, neutrophil apoptosis can be accelerated both in the presence and in the absence of survival factors by activation of distinct members of the tumor necrosis factor/nerve growth factor receptor family. This review focuses on recently published work regarding signaling pathways that regulate neutrophil apoptosis.