GRANULOCYTE APOPTOSIS AND INFLAMMATORY DISEASE

We have described a novel pathway available for the clearance of extra vasated granulocytes whereby the cells undergo apoptosis, a process wh ich 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. Th us, by contrast with a granulocyte fate involving necrosis, apoptosis is likely to represent an injury limiting tissue removal process for g ranulocytes which would tend to promote resolution processes. It is sp eculated that dysregulation of this process or an imbalance between it and necrotic pathways may be important in inflammatory disease pathog enesis. Whether or not this is the case, the apoptotic mechanisms avai lable in neutrophil and eosinophil granulocytes provide opportunities for the selective induction of apoptosis in specific inflammatory cell s in what may represent novel therapeutic approaches to inflammatory d isease.