title: Expansion of the neonatal platelet mass is achieved via an extension of platelet lifespan.
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.
authors.affiliation: Division of Newborn Medicine, Boston Children's Hospital, Boston, MA;
authors.forename: Zhi-Jian
authors.initials: ZJ
authors.lastname: Liu
authors.affiliation: Division of Translational Medicine, Brigham and Women's Hospital, Boston, MA;
authors.forename: Karin M
authors.initials: KM
authors.lastname: Hoffmeister
authors.affiliation: Division of Neonatology, University of Florida, Gainesville, FL;
authors.forename: Zhongbo
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY;
authors.forename: Donald E
authors.initials: DE
authors.lastname: Mager
authors.affiliation: Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY;
authors.forename: Sihem
authors.initials: S
authors.lastname: Ait-Oudhia
authors.affiliation: Cancer and Hematology Division, The Walter and Eliza Hall Institute of Medical Research, and the Department of Medical Biology, University of Melbourne, Parkville, Australia;
authors.forename: Marlyse A
authors.initials: MA
authors.lastname: Debrincat
authors.affiliation: Cancer and Hematology Division, The Walter and Eliza Hall Institute of Medical Research, and the Department of Medical Biology, University of Melbourne, Parkville, Australia;
authors.forename: Irina
authors.initials: I
authors.lastname: Pleines
authors.affiliation: Cancer and Hematology Division, The Walter and Eliza Hall Institute of Medical Research, and the Department of Medical Biology, University of Melbourne, Parkville, Australia;
authors.forename: Emma C
authors.initials: EC
authors.lastname: Josefsson
authors.affiliation: Cancer and Hematology Division, The Walter and Eliza Hall Institute of Medical Research, and the Department of Medical Biology, University of Melbourne, Parkville, Australia;
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Kile
authors.affiliation: Division of Translational Medicine, Brigham and Women's Hospital, Boston, MA; Division of Hematology, Brigham and Women's Hospital and the Vascular Biology Program, Boston Children's Hospital, Boston, MA; and.
authors.forename: Joseph
authors.initials: J
authors.lastname: Italiano
authors.affiliation: Division of Newborn Medicine, Boston Children's Hospital, Boston, MA;
authors.forename: Haley
authors.initials: H
authors.lastname: Ramsey
authors.affiliation: Division of Translational Medicine, Brigham and Women's Hospital, Boston, MA;
authors.forename: Renata
authors.initials: R
authors.lastname: Grozovsky
authors.affiliation: College of Pharmacy, University of Iowa, Iowa City, IA.
authors.forename: Peter
authors.initials: P
authors.lastname: Veng-Pedersen
authors.affiliation: Division of Newborn Medicine, Boston Children's Hospital, Boston, MA;
authors.forename: Chaitanya
authors.initials: C
authors.lastname: Chavda
authors.affiliation: Division of Newborn Medicine, Boston Children's Hospital, Boston, MA;
authors.forename: Martha
authors.initials: M
authors.lastname: Sola-Visner
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007231:Infant, Newborn; D008099:Liver / Q000166:cytology; D063847:Mean Platelet Volume; D008533:Megakaryocytes / Q000502:physiology / Q000648:ultrastructure; D051379:Mice; D009596:Nitrophenols / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D010976:Platelet Count; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D013449:Sulfonamides / Q000494:pharmacology; D034061:Thrombopoiesis / Q000187:drug effects / Q000502:physiology*
chemical_list: C501332:ABT-737; D001713:Biphenyl Compounds; D009596:Nitrophenols; D010879:Piperazines; D019253:Proto-Oncogene Proteins c-bcl-2; D013449:Sulfonamides