Evidence for a pro-apoptotic function of CD137 in granulocytes.

Granulocyte apoptosis is crucial for controlling granulocyte number under normal and inflammatory conditions. Reduced apoptosis of different types of granulocytes is one important mechanism for cell accumulation. Which granulocyte subtype expands is largely dependent on the cytokine milieu present at the inflammatory site. Over expression of G-CSF and GM-CSF is associated with neutrophilia, whereas over expression of IL-5 is linked to eosinophilia. Cytokine withdrawal leads to the induction of granulocyte apoptosis, a mechanism which occurs during resolution of inflammation. Besides survival factors, granulocyte apoptosis is also regulated by death factors, which belong to the tumor necrosis factor (TNF)/nerve growth factor (NGF) superfamily. Recent observations suggest that granulocytes can be activated via CD137, a member of the TNF/NGF receptor superfamily. This review summarizes our current knowledge on the potential role of CD137 in the regulation of both neutrophil and eosinophil apoptosis.