Programmed Anuclear Cell Death Delimits Platelet Life Span

Platelets are anuclear cytoplasmic fragments essential for blood clotting and wound healing. Despite much speculation, the factors determining their life span in the circulation are unknown. We show here that an intrinsic program for apoptosis controls platelet survival and dictates their life span....

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Bibliographic Details
Published in:Cell 2007-03, Vol.128 (6), p.1173-1186
Main Authors: Mason, Kylie D., Carpinelli, Marina R., Fletcher, Jamie I., Collinge, Janelle E., Hilton, Adrienne A., Ellis, Sarah, Kelly, Priscilla N., Ekert, Paul G., Metcalf, Donald, Roberts, Andrew W., Huang, David C.S., Kile, Benjamin T.
Format: Article
Language:English
Subjects:
Animals
Apoptosis
bcl-2 Homologous Antagonist-Killer Protein - genetics
bcl-2 Homologous Antagonist-Killer Protein - metabolism
bcl-X Protein - antagonists & inhibitors
bcl-X Protein - chemistry
bcl-X Protein - genetics
bcl-X Protein - metabolism
Biomimetics
Biphenyl Compounds - pharmacology
Blood Platelets - cytology
Caspases - metabolism
Cell Nucleus - metabolism
CELLBIO
Crosses, Genetic
Ethylnitrosourea - pharmacology
Female
HUMDISEASE
Male
Mice
Mice, Inbred BALB C
Models, Molecular
Mutagenesis - drug effects
Nitrophenols - pharmacology
Piperazines - pharmacology
Protein Structure, Tertiary
Sulfonamides - pharmacology
Thrombocytopenia - chemically induced
Thrombocytopenia - genetics
Thrombocytopenia - metabolism
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Summary:Platelets are anuclear cytoplasmic fragments essential for blood clotting and wound healing. Despite much speculation, the factors determining their life span in the circulation are unknown. We show here that an intrinsic program for apoptosis controls platelet survival and dictates their life span. Pro-survival Bcl-xL constrains the pro-apoptotic activity of Bak to maintain platelet survival, but as Bcl-xL degrades, aged platelets are primed for cell death. Genetic ablation or pharmacological inactivation of Bcl-xL reduces platelet half-life and causes thrombocytopenia in a dose-dependent manner. Deletion of Bak corrects these defects, and platelets from Bak-deficient mice live longer than normal. Thus, platelets are, by default, genetically programmed to die by apoptosis. The antagonistic balance between Bcl-xL and Bak constitutes a molecular clock that determines platelet life span: this represents an important paradigm for cellular homeostasis, and has profound implications for the diagnosis and treatment of disorders that affect platelet number and function.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2007.01.037