Faculty Collaboration Database

Expansion of the neonatal platelet mass is achieved via an extension of platelet lifespan. Blood 2014 May 29;123(22):3381-9

Date

03/07/2014

Pubmed ID

24599546

Pubmed Central ID

PMC4041172

DOI

10.1182/blood-2013-06-508200

Scopus ID

2-s2.0-84901722801 (requires institutional sign-in at Scopus site)   67 Citations

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 sevenfold during the first 2 weeks of murine life, a time during which thrombopoiesis shifted from liver to bone marrow. Studies applying in vivo biotinylation and mathematical modeling showed that newborn and adult mice had similar platelet production rates, but neonatal platelets survived 1 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 showed 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.

Author List

Liu ZJ, Hoffmeister KM, Hu Z, Mager DE, Ait-Oudhia S, Debrincat MA, Pleines I, Josefsson EC, Kile BT, Italiano J Jr, Ramsey H, Grozovsky R, Veng-Pedersen P, Chavda C, Sola-Visner M

Author

Karin Hoffmeister MD Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Animals, Newborn
Apoptosis
Biphenyl Compounds
Blood Platelets
Cell Survival
Humans
Infant, Newborn
Liver
Mean Platelet Volume
Megakaryocytes
Mice
Nitrophenols
Piperazines
Platelet Count
Proto-Oncogene Proteins c-bcl-2
Spleen
Sulfonamides
Thrombopoiesis