Granulocyte apoptosis is a crucial part of the successful resolution of inflammation. In vitro results show that activation of NF-κB (nuclear factor κB) in granulocytes is a survival mechanism. NF-κB inhibitors increase the rate of constitutive apoptosis in neutrophils and eosinophils and cause these cells to respond to the pro-apoptotic effects of TNF-α (tumour necrosis factor-α). Results from both in vivo and in vitro experiments suggest that there are at least two important waves of NF-κB activation in inflammatory loci, which increase the expression of COX-2 (cyclooxygenase-2), itself an NF-κB controlled gene. The first wave causes the production of inflammatory mediators such as PGE2 (prostaglandin E2), allowing the establishment of inflammation. The second wave causes the synthesis of PGD2 and its metabolites that induce granulocyte apoptosis by inhibiting NF-κB activation. These metabolites may therefore be important physiological mediators controlling the resolution of inflammation. Although NF-κB is an important target for anti-inflammatory therapy, the timing of inhibition in vivo may be crucial, to ensure that production of PGD2 and its sequential metabolites can occur.

Abbreviations used: AA, arachidonic acid; COX, cyclooxygenase; NF-κB, nuclear factor κB; IκB, inhibitor of NF-κB; PG, prostaglandin; TNF, tumour necrosis factor.

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Author notes

Apoptosis in Myeloid Cells: Molecular Insights into Disease Processes: a Biochemical Society Focused Meeting held at New Edinburgh Royal Infirmary, Little France, Nr. Edinburgh, 19–20 November 2003