RRC ID 43157
Author Hu H, Shikama Y, Matsuoka I, Kimura J.
Title Terminally differentiated neutrophils predominantly express Survivin-2 alpha, a dominant-negative isoform of survivin.
Journal J. Leukoc. Biol.
Abstract Survivin, which is a member of the inhibitor of apoptosis protein family, was found originally in immature cells and cancer cells but not in non-neoplastic adult tissues. The subsequent identification of four other alternative splice variants that possess distinct functions and localizations suggested the diverse roles of survivin isoforms. An unspecified isoform of survivin was found recently to be induced in terminally differentiated neutrophils by cytokines that prolong the neutrophil lifespan, such as GM-CSF and G-CSF, suggesting the importance of survivin in blocking apoptosis in neutrophils. To examine the mechanism by which survivin inhibits neutrophil apoptosis, we attempted to induce survivin by GM-CSF/G-CSF in an HL60 cell line that was differentiated into neutrophils by all-trans retinoic acid and DMSO and freshly isolated human neutrophils. The antiapoptotic isoform "Survivin," which was decreased during differentiation, was re-induced by GM-CSF in neutrophil-like, differentiated HL60. In contrast, in normal neutrophils, survivin mRNA was observed to increase spontaneously after 24 h incubation, and no additional elevation was induced by GM-CSF/G-CSF, which exerted their antiapoptotic effects on the neutrophils in 6 h, despite the lack of survivin induction. PCR and Western blotting detected Survivin-2 alpha, a dominant-negative of antiapoptotic Survivin, with no other isoforms in the freshly isolated or incubated neutrophils. Our study revealed that the expressed isoforms and the response to GM-CSF were different between the HL60-derived and normal neutrophils, which predominantly expressed Survivin-2 alpha, not likely involved in apoptosis inhibition by GM-CSF/G-CSF.
Volume 83(2)
Pages 393-400
Published 2008-2
DOI 10.1189/jlb.0507282
PII jlb.0507282
PMID 17965335
MeSH Adult Apoptosis / drug effects Apoptosis / physiology Base Sequence Cell Differentiation Dimethyl Sulfoxide / pharmacology Exons / genetics Gene Expression Regulation / drug effects Gene Expression Regulation, Leukemic / drug effects Genes, Dominant Granulocyte Colony-Stimulating Factor / pharmacology Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology HL-60 Cells / cytology HL-60 Cells / drug effects HL-60 Cells / metabolism Humans Inhibitor of Apoptosis Proteins Leukemia, Promyelocytic, Acute / pathology Microtubule-Associated Proteins / biosynthesis* Microtubule-Associated Proteins / chemistry Microtubule-Associated Proteins / genetics Microtubule-Associated Proteins / physiology Molecular Sequence Data Neoplasm Proteins / biosynthesis* Neoplasm Proteins / chemistry Neoplasm Proteins / genetics Neoplasm Proteins / physiology Neutrophils / cytology Neutrophils / drug effects* Neutrophils / metabolism Protein Isoforms / biosynthesis Protein Isoforms / chemistry Protein Isoforms / genetics Protein Isoforms / physiology Survivin Tretinoin / pharmacology
IF 4.224
Times Cited 12
Human and Animal Cells