Bcl-2 family expression in human neutrophils during delayed and accelerated apoptosis

The human neutrophil spontaneously undergoes apoptosis, but this type of ce ll death can be delayed or accelerated by a wide variety of agents. There a re wide discrepancies in the literature regarding the expression of the Bcl -2 family of proteins in human neutrophils. Here, we show that Al, Mcl-1, B el-X-L, and Bad are major transcripts in human neutrophils and that levels of these transcripts are cytokine regulated. However, no Bel-XL protein was detected in Western blots. Protein levels for the proapoptotic proteins Ba d, Bax, Bali., and Bik. remained constant during culture, despite changes i n the levels of mRNA for these gene products. These proapoptotic proteins w ere extremely stable, having very long half-lives. In contrast, Al and Mcl- 1 transcripts were extremely unstable (with similar to3-h half-lives), and Mcl-1 protein was also subject to rapid turnover. These results indicate th at neutrophil survival is regulated by the inducible expression of the shor t-lived Mcl-1 and possibly the Al gene products. In the absence of their co ntinued expression, these prosurvival gene products are rapidly turned over , and then the activity of the stable death proteins predominates and promo tes apoptosis.