Relevance of granulocyte apoptosis to resolution of inflammation at the respiratory mucosa

Leitch, A E; Duffin, R; Haslett, C; Rossi, A G

The respiratory mucosa is responsible for gas exchange and is therefore, of necessity, exposed to airborne pathogens, allergens, and foreign particles. It has evolved a multi-faceted, physical and immune defense system to ensure that in the majority of instances, potentially injurious invaders are repelled. Inflammation, predominantly mediated by effector cells of the granulocyte lineage including neutrophils and eosinophils, is a form of immune defense. Where inflammation proves unable to remove an inciting stimulus, chronic inflammatory disease may supervene because of the potential for tissue damage conferred by the presence of large numbers of frustrated, activated granulocytes. Successful recovery from inflammatory disease and resolution of inflammation rely on the clearance of these cells. Ideally, they should undergo apoptosis prior to phagocytosis by macrophage, dendritic, or epithelial cells. The outcome of inflammation can have serious sequelae for the integrity of the respiratory mucosa leading to disease. Therapeutic strategies to drive resolution of inflammation may be directed at the induction of granulocyte apoptosis and the enhancement of granulocyte clearance. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/mi.2008.31) contains supplementary material, which is available to authorized users.