Human neutrophil kinetics: modeling of stable isotope labeling data supports short blood neutrophil half-lives
| Autor: | Arafa Salam, Yan Zhang, Becca Asquith, Christoph Niederalt, Michael Block, Marjet Elemans, Julio Lahoz-Beneytez, Derek C. Macallan, Raya Ahmed |
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| Přispěvatelé: | Commission of the European Communities, LEUKAEMIA & LYMPHOMA RESEARCH, Bloodwise (formerly LLR), Wellcome Trust, Medical Research Council (MRC) |
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine CLEARANCE Neutrophils MOUSE Blood neutrophil Biochemistry 0302 clinical medicine Granulocyte Precursor Cells 1102 Cardiorespiratory Medicine and Haematology IN-VIVO Hematology Half-life COLONY-STIMULATING FACTOR Middle Aged 3. Good health Isotope Labeling Female Life Sciences & Biomedicine Half-Life Adult medicine.medical_specialty Human neutrophil Immunology Kinetics Carbohydrate metabolism Biology Models Biological MATURATION CELL-PROLIFERATION Andrology 03 medical and health sciences In vivo Internal medicine medicine CELLULARITY Humans RATES Science & Technology 1103 Clinical Sciences DNA Cell Biology Deuterium Glucose 030104 developmental biology 1114 Paediatrics and Reproductive Medicine Stable Isotope Labeling HUMAN BONE-MARROW 030215 immunology |
| Zdroj: | Blood. 127:3431-3438 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2016-03-700336 |
| Popis: | Human neutrophils have traditionally been thought to have a short half-life in blood; estimates vary from 4 to 18 hours. This dogma was recently challenged by stable isotope labeling studies with heavy water, which yielded estimates in excess of 3 days. To investigate this disparity, we generated new stable isotope labeling data in healthy adult subjects using both heavy water (n = 4) and deuterium-labeled glucose (n = 9), a compound with more rapid labeling kinetics. To interpret results, we developed a novel mechanistic model and applied it to previously published (n = 5) and newly generated data. We initially constrained the ratio of the blood neutrophil pool to the marrow precursor pool (ratio = 0.26; from published values). Analysis of heavy water data sets yielded turnover rates consistent with a short blood half-life, but parameters, particularly marrow transit time, were poorly defined. Analysis of glucose-labeling data yielded more precise estimates of half-life (0.79 ± 0.25 days; 19 hours) and marrow transit time (5.80 ± 0.42 days). Substitution of this marrow transit time in the heavy water analysis gave a better-defined blood half-life of 0.77 ± 0.14 days (18.5 hours), close to glucose-derived values. Allowing the ratio of blood neutrophils to mitotic neutrophil precursors (R) to vary yielded a best-fit value of 0.19. Reanalysis of the previously published model and data also revealed the origin of their long estimates for neutrophil half-life: an implicit assumption that R is very large, which is physiologically untenable. We conclude that stable isotope labeling in healthy humans is consistent with a blood neutrophil half-life of less than 1 day. |
| Databáze: | OpenAIRE |
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