Age-Dependent Control of Collagen-Dependent Platelet Responses by Thrombospondin-1-Comparative Analysis of Platelets from Neonates, Children, Adolescents, and Adults.

Autor:	Herken K; Department of Anaesthesiology, Intensive Care and Pain Medicine, Experimental and Clinical Haemostasis, University Hospital of Münster, 48149 Münster, Germany., Glauner M; Department of Anaesthesiology, Intensive Care and Pain Medicine, Experimental and Clinical Haemostasis, University Hospital of Münster, 48149 Münster, Germany.; DSM Nutritional Products, Branch Pentapharm, 4147 Aesch, Switzerland., Robert SC; Department of Anaesthesiology, Intensive Care and Pain Medicine, Experimental and Clinical Haemostasis, University Hospital of Münster, 48149 Münster, Germany., Maas M; Department of Anaesthesiology, Intensive Care and Pain Medicine, Experimental and Clinical Haemostasis, University Hospital of Münster, 48149 Münster, Germany.; Fachklinik Hornheide, Department for Anaesthesiology, Intensive Care and Pain Medicine, 48157 Münster, Germany., Zippel S; Department of Anaesthesiology, Intensive Care and Pain Medicine, Experimental and Clinical Haemostasis, University Hospital of Münster, 48149 Münster, Germany., Nowak-Göttl U; Department of Paediatric Haematology/Oncology, University of Münster, 48149 Münster, Germany.; Institute of Clinical Chemistry, University Hospital Kiel-Lübeck, 24118 Kiel, Germany., Zieger B; Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany., Lahav J; Hemostasis Laboratory, Rabin Medical Center-Beilinson Hospital, 49100 Petah-Tikva, Israel.; Department of Human Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, 39040 Tel Aviv, Israel., Fender AC; Department of Anaesthesiology, Intensive Care and Pain Medicine, Experimental and Clinical Haemostasis, University Hospital of Münster, 48149 Münster, Germany.; Institute of Pharmacology, West German Heart and Vascular Center, University of Duisburg-Essen, 45147 Essen, Germany., Jurk K; Department of Anaesthesiology, Intensive Care and Pain Medicine, Experimental and Clinical Haemostasis, University Hospital of Münster, 48149 Münster, Germany.; Center for Thrombosis and Hemostasis (CTH), University Medical Center, Johannes Gutenberg-University Mainz, 55131 Mainz, Germany., Kehrel BE; Department of Anaesthesiology, Intensive Care and Pain Medicine, Experimental and Clinical Haemostasis, University Hospital of Münster, 48149 Münster, Germany.
Jazyk:	angličtina
Zdroj:	International journal of molecular sciences [Int J Mol Sci] 2021 May 05; Vol. 22 (9). Date of Electronic Publication: 2021 May 05.
DOI:	10.3390/ijms22094883
Abstrakt:	Platelet function is developmentally regulated. Healthy neonates do not spontaneously bleed, but their platelets are hypo-reactive to several agonists. The mechanisms underlying immature platelet function in neonates are incompletely understood. This critical issue remains challenging for the establishment of age-specific reference ranges. In this study, we evaluated platelet reactivity of five pediatric age categories, ranging from healthy full-term neonates up to adolescents (11-18 years) in comparison to healthy adults (>18 years) by flow cytometry. We confirmed that platelet hypo-reactivity detected by fibrinogen binding, P-selectin, and CD63 surface expression was most pronounced in neonates compared to other pediatric age groups. However, maturation of platelet responsiveness varied with age, agonist, and activation marker. In contrast to TRAP and ADP, collagen-induced platelet activation was nearly absent in neonates. Granule secretion markedly remained impaired at least up to 10 years of age compared to adults. We show for the first time that neonatal platelets are deficient in thrombospondin-1, and exogenous platelet-derived thrombospondin-1 allows platelet responsiveness to collagen. Platelets from all pediatric age groups normally responded to the C-terminal thrombospondin-1 peptide RFYVVMWK. Thus, thrombospondin-1 deficiency of neonatal platelets might contribute to the relatively impaired response to collagen, and platelet-derived thrombospondin-1 may control distinct collagen-induced platelet responses.
Databáze:	MEDLINE
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