Expansion of the neonatal platelet mass is achieved via an extension of platelet lifespan.
- Author(s)
- Liu, ZJ; Hoffmeister, K; Hu, Z; Mager, DE; Ait-Oudhia, S; Debrincat, MA; Pleines, I; Josefsson, EC; Kile, BT; Italiano, J; Ramsey, H; Grozovsky, R; Veng-Pedersen, P; Chavda, C; Sola-Visner, M;
- Details
- Publication Year 2014-03-05,Volume 123,Issue #22,Page 3381-3389
- Journal Title
- Blood
- Publication Type
- JOURNAL ARTICLE
- Abstract
- The fetal/neonatal hematopoietic system must generate enough blood cells to meet the demands of rapid growth. This unique challenge might underlie the high incidence of thrombocytopenia among preterm neonates. In this study, neonatal platelet production and turnover were investigated in newborn mice. Based on a combination of blood volume expansion and increasing platelet counts, the platelet mass increased 7-fold during the first two weeks of murine life, a time during which thrombopoiesis shifted from liver to bone marrow. Studies applying in-vivo biotinylation and mathematical modeling revealed that newborn and adult mice had similar platelet production rates, but neonatal platelets survived one day longer in circulation. This prolonged lifespan fully accounted for the rise in platelet counts observed during the second week of murine postnatal life. A study of pro-apoptotic and anti-apoptotic Bcl-2 family proteins found that neonatal platelets had higher levels of the anti-apoptotic protein Bcl-2 and were more resistant to apoptosis induced by the Bcl-2/Bcl-xL inhibitor ABT-737 than adult platelets. However, genetic ablation or pharmacologic inhibition of Bcl-2 alone did not shorten neonatal platelet survival or reduce platelet counts in newborn mice, indicating the existence of redundant or alternative mechanisms mediating the prolonged lifespan of neonatal platelets.
- Publisher
- AMER SOC HEMATOLOGY
- Research Division(s)
- Cancer And Haematology
- Publisher's Version
- https://doi.org/10.1182/blood-2013-06-508200
- Terms of Use/Rights Notice
- Copyright © 2014 American Society of Hematology
Creation Date: 2014-03-13 11:57:23