Granulocytes are terminally differentiated cells generated in the bone marrow under the influence of various cytokines. They are important components of the natural defense system. Under normal circumstances, granulocytes have a very short life span that does not exceed more than 2–3 days. One mechanism to accumulate granulocytes at sites of inflammation is delayed apoptosis, which is at least partially mediated by overexpression of cytokines.1 In many chronic inflammatory responses, such as lung fibrosis or bronchial asthma, granulocytes (neutrophils and/or eosinophils) cause unwanted tissue damage via the release of toxic mediators. Clearly, induction of granulocyte apoptosis would help to limit tissue damage and to reduce inflammation in these cases. Therefore, investigating the molecular control of granulocyte apoptosis under normal and inflammatory conditions may lead to the identification of new therapeutic drug targets.

Besides Bax, another pro-apoptotic member of the Bcl-2 family, Bim, has recently been implicated in apoptosis mediated by growth factor withdrawal in a mouse IL-3 dependent cell line as well as in primary mouse fetal liver cells.5 Whether Bim plays a role in the induction of spontaneous apoptosis of granulocytes remains to be investigated. Granulocytes may increase Bim levels in the absence of survival factors leading to the neutralization of pro-survival members of the Bcl-2 family (Figure 1A).5 Interestingly, both Bim5 and Fas ligand6 are under the control of forkhead transcription factor FKHR-L1. However, there is only little evidence to suggest that Fas ligand is upregulated in granulocytes cultured in the absence of survival factors in vitro.7

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