The function and fate of neutrophils at the inflamed site: prospects for therapeutic intervention

Neutrophils play a key role in the immediate nonspecific immune response, a nd defects in their function increase host susceptibility to a range of inf ective agents. However, excess activation and/or delayed clearance of these cells from an inflamed site can lead to significant tissue damage. Neutrop hil priming by agents such as endotoxin, granulocyte macrophage colony stim ulating factor (CM-CSF), platelet activating factor (PAF) and tumour necros is factor-alpha (TNF alpha) may play a pivotal role in modulating the adhes ive and secretory properties of these cells. Priming also appears to affect the survival of neutrophils by delaying constitutive apoptosis. The unique signal transduction events that control neutrophil priming and apoptosis, and particularly the importance of the phospholipase C and phosphoinositide 3-kinase pathways, suggest opportunities for selective pharmacological int ervention.