Lahoz-Beneytez, J; Elemans, M; Zhang, Y; Ahmed, R; Salam, A; Block, M; Niederalt, C; Asquith, B; Macallan, D
(2016)
Human neutrophil kinetics: modeling of stable isotope labeling data supports short blood neutrophil half-lives.
Blood, 127.
pp. 3431-3438.
ISSN 1528-0020
https://doi.org/10.1182/blood-2016-03-700336
SGUL Authors: Macallan, Derek Clive Zhang, Yan
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Abstract
Human neutrophils have traditionally been thought to have a short half-life in blood; estimates vary from 4-18 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. We applied this model to both previously-published (n=5) and newly-generated data. We initially constrained the ratio of the blood neutrophil pool to the marrow precursor pool (R=0.26, from published values). Analysis of heavy water datasets 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, 0.77 ± 0.14 days (18.5 hours), close to glucose-derived values. Allowing R to vary yielded a best-fit value, R=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 one day.
Item Type: | Article | ||||||||||||
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Additional Information: | © The American Society of Hematology. For personal use only. This research was originally published in Blood. Lahoz-Beneytez, J.; Elemans, M.; Zhang, Y.; Ahmed, R.; Salam, A.; Block, M.; Niederalt, C.; Asquith, B.; Macallan, D.. Human neutrophil kinetics: modeling of stable isotope labeling data supports short blood neutrophil half-lives. Blood. 2016; Vol 127: pp-pp 3431-3438. | ||||||||||||
Keywords: | Immunology, 1102 Cardiovascular Medicine And Haematology, 1103 Clinical Sciences, 1114 Paediatrics And Reproductive Medicine | ||||||||||||
SGUL Research Institute / Research Centre: | Academic Structure > Infection and Immunity Research Institute (INII) | ||||||||||||
Journal or Publication Title: | Blood | ||||||||||||
ISSN: | 1528-0020 | ||||||||||||
Language: | ENG | ||||||||||||
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Publisher License: | Publisher's own licence | ||||||||||||
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PubMed ID: | 27136946 | ||||||||||||
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URI: | https://openaccess.sgul.ac.uk/id/eprint/107958 | ||||||||||||
Publisher's version: | https://doi.org/10.1182/blood-2016-03-700336 |
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