Abstract
We have described a novel pathway available for the clearance of extravasated granulocytes whereby the cells undergo apoptosis, a process which controls the functional longevity of granulocytes in situ and the rate of which is modulated by external and internal control mechanisms. It leads to shut-down of the secretory processes and recognition of the intact senescent cell by a novel macrophage recognition mechanism which fails to stimulate the release of pro-inflammatory mediators. Thus, by contrast with a granulocyte fate involving necrosis, apoptosis is likely to represent an injury limiting tissue removal process for granulocytes which would tend to promote resolution processes. It is speculated that dysregulation of this process or an imbalance between it and necrotic pathways may be important in inflammatory disease pathogenesis. Whether or not this is the case, the apoptotic mechanisms available in neutrophil and eosinophil granulocytes provide opportunities for the selective induction of apoptosis in specific inflammatory cells in what may represent novel therapeutic approaches to inflammatory disease.