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          Institute: MPI für molekulare Biomedizin     Collection: Jahrbuch 2018 (publ. 2017, arch)     Display Documents



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ID: 744124.0, MPI für molekulare Biomedizin / Jahrbuch 2018 (publ. 2017, arch)
Maturation of Platelet Function During Murine Fetal Development In Vivo
Authors:Margraf, A.; Nussbaum, C.; Rohwedder, I.; Klapproth, S.; Kurz, A. R. M.; Florian, A.; Wiebking, V.; Pircher, J.; Pruenster, M.; Immler, R.; Dietzel, S.; Kremer, L.; Kiefer, F.; Moser, M.; Flemmer, A. W.; Quackenbush, E.; von Andrian, U. H.; Sperandio, M.
Date of Publication (YYYY-MM-DD):2017-06
Title of Journal:Arterioscler Thromb Vasc Biol
Volume:37
Issue / Number:6
Start Page:1076
End Page:1086
Review Status:Internal review
Audience:Not Specified
Abstract / Description:OBJECTIVE: Platelet function has been intensively studied in the adult organism. However, little is known about the function and hemostatic capacity of platelets in the developing fetus as suitable in vivo models are lacking. APPROACH AND RESULTS: To examine fetal platelet function in vivo, we generated a fetal thrombosis model and investigated light/dye-induced thrombus formation by intravital microscopy throughout gestation. We observed that significantly less and unstable thrombi were formed at embryonic day (E) 13.5 compared with E17.5. Flow cytometry revealed significantly lower platelet counts in E13.5 versus E17.5 fetuses versus adult controls. In addition, fetal platelets demonstrated changed activation responses of surface adhesion molecules and reduced P-selectin content and mobilization. Interestingly, we also measured reduced levels of the integrin-activating proteins Kindlin-3, Talin-1, and Rap1 during fetal development. Consistently, fetal platelets demonstrated diminished spreading capacity compared with adults. Transfusion of adult platelets into the fetal circulation led to rapid platelet aggregate formation even in young fetuses. Yet, retrospective data analysis of a neonatal cohort demonstrated no correlation of platelet transfusion with closure of a persistent ductus arteriosus, a process reported to be platelet dependent. CONCLUSIONS: Taken together, we demonstrate an ontogenetic regulation of platelet function in vivo with physiologically low platelet numbers and hyporeactivity early during fetal development shedding new light on hemostatic function during fetal life.
Free Keywords:Animals; Blood Platelets/*metabolism; Cell Adhesion Molecules/blood; Databases, Factual; Disease Models, Animal; Ductus Arteriosus, Patent/blood; Female; Gestational Age; Green Fluorescent Proteins/genetics/metabolism; *Hemostasis; Humans; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Mice, Inbred C57BL; Mice, Transgenic; *Platelet Activation; Platelet Adhesiveness; Platelet Transfusion; Premature Birth/blood; Retrospective Studies; Signal Transduction; Thrombocytopenia/blood; Thrombosis/*blood; blood platelets; fetal development; hemostasis; intravital microscopy; microcirculation; thrombosis
External Publication Status:published
Document Type:Article
Communicated by:MPI für molekulare Biomedizin
Affiliations:MPI für molekulare Biomedizin
External Affiliations:From the Walter Brendel Centre of Experimental Medicine, Munich, Germany (A.M., C.N., I.R., S.K., A.R.M.K., A.F., J.P., M.P., R.I., S.D., M.S.); Division of Neonatology, Hauner Children's University Hospital and Perinatal Centre, Ludwig Maximilians University, Munich, Germany (C.N., A.F., V.W., A.W.F.); Medizinische Klinik und Poliklinik I, Klinikum der Ludwig Maximilians Universitat, Munich, Germany (J.P.); Max Planck Institute for Molecular Biomedicine, Munster, Germany (L.K., F.K.); Max PIanck Institute of Biochemistry, Department of Molecular Medicine, Martinsried, Germany (M.M.); Roche Inc, New York, NY (E.Q.); and Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA (U.H.v.A.). markus.sperandio@lmu.de.
Identifiers:ISSN:1524-4636 (Electronic) 1079-5642 (Linking) %R 10.1... [ID No:1]
URL:https://www.ncbi.nlm.nih.gov/pubmed/28428216 [ID No:2]
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