Targeting apoptosis in the control of inflammation.

Abstract

Apoptosis is the most common form of physiological cell death and serves to eliminate cells that are genomically altered and therefore potentially harmful to the body, senescent or become replaced by functionally different cell types. It is defined by morphological criteria, including chromatin condensation, nuclear fragmentation, plasma membrane blebbing, organelle disruption, loss of adhesion and rounding (in adherent cells), and cell shrinkage. Apoptosis is required for normal development and maintenance of tissue homeostasis, and its dysregulation is associated with various pathological conditions. For instance, there is often too little apoptosis in cancer and there is usually too much apoptosis in neurodegeneration and acquired immune deficiency syndrome. In inflammatory responses, delayed apoptosis of inflammatory cells contributes to their accumulation in order to efficiently eliminate the pathogen. This article provides a short overview regarding dysregulated apoptosis associated with inflammation. Delayed neutrophil apoptosis has been associated with several acute and chronic inflammatory diseases ( e.g. pneumonia, sepsis, cystic fibrosis) and appears to be largely mediated by excessive production of granulocyte colony­stimulating factor and granulocyte/macrophage colony­stimulating factor (GM‐CSF) 1. The induction of neutrophil apoptosis during the resolution of a neutrophilic inflammatory response can be mimicked in vitro by culturing the cells in the absence of sufficient concentrations of survival factors, a process called spontaneous apoptosis. Most studies have been performed on purified blood neutrophils, aiming to understand the molecular events that control apoptosis in these cells. Tyrosine kinases, the phosphoinositide 3‐kinase …