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BCL‐2 family expression in human neutrophils during delayed and accelerated apoptosis
Author(s) -
Moulding Dale A.,
Akgul Cahit,
Derouet Mathieu,
White Michael R. H.,
Edwards Steven W.
Publication year - 2001
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.70.5.783
Subject(s) - biology , apoptosis , bcl xl , programmed cell death , messenger rna , gene , gene expression , bcl 2 family , microbiology and biotechnology , blot , gene family , genetics
The human neutrophil spontaneously undergoes apoptosis, but this type of cell death can be delayed or accelerated by a wide variety of agents. There are wide discrepancies in the literature regarding the expression of the Bcl‐2 family of proteins in human neutrophils. Here, we show that A1, Mcl‐1, Bcl‐X L , and Bad are major transcripts in human neutrophils and that levels of these transcripts are cytokine regulated. However, no Bcl‐X L protein was detected in Western blots. Protein levels for the proapoptotic proteins Bad, Bax, Bak, and Bik remained constant during culture, despite changes in the levels of mRNA for these gene products. These proapoptotic proteins were extremely stable, having very long half‐lives. In contrast, A1 and Mcl‐1 transcripts were extremely unstable (with ∼3‐h half‐lives), and Mcl‐1 protein was also subject to rapid turnover. These results indicate that neutrophil survival is regulated by the inducible expression of the short‐lived Mcl‐1 and possibly the A1 gene products. In the absence of their continued expression, these prosurvival gene products are rapidly turned over, and then the activity of the stable death proteins predominates and promotes apoptosis.