archives@tulane.edu / Neutrophils are the most abundant white blood cells in human blood and require continuous replenishment from bone marrow granulopoiesis throughout life. Their function as phagocytes in innate immunity has been well studied, but the dynamics and movement of neutrophils in vivo are less clearly understood. To quantitate the kinetics of neutrophil movement during homeostasis, acute inflammation, and aging, we applied 5-bromo-2'-deoxyuridine (BrdU) pulse-chase labeling followed by hematology and flow cytometry analyses in healthy, acutely-infected, and aged rhesus macaques (Macaca mulatta). We applied our kinetics results to a mathematical model and calculated that neutrophils have a half-life of 1.63 ± 0.16 days and a daily production of 1.42×109 cells / L / day in heathy young adult rhesus macaques. In rhesus macaques undergoing acute inflammation, we followed neutrophil kinetics during acute stages of a bacterial infection (Shigella) and viral infection (SIV). A massive replenishment of neutrophils from bone marrow to blood as indicated by BrdU kinetics occurred as early as 3 days post Shigella inoculation, the degree to which correlated with the Shigella inoculation doses. As animals aged, neutrophil production declined while plasma G-CSF levels increased, and there was an earlier release, as well as higher in-group variability in neutrophil kinetics, particularly upon reaching 20 years of age or older (equivalent to 70 years or more in humans). This suggested a dysregulated feedback mechanism whereby increased levels of G-CSF failed to restore neutrophil production in elderly rhesus macaques that was associated with induced production of pro-inflammatory cytokines and earlier release of less mature neutrophils and PMN-MDSCs. Taken together, we established a rhesus macaque model to study neutrophil kinetics and functions in vivo during homeostasis, acute inflammation, and aging. Our results emphasized the massive production of neutrophils during homeostasis and the continuous requirement but reduced replenishment capabilities during aging. The significance of the results also indicates an important role for these long-discovered leukocytes in maintaining homeostasis beyond phagocytic pathogen clearance. / 1 / Ziyuan He
| Identifer | oai:union.ndltd.org:TULANE/oai:http://digitallibrary.tulane.edu/:tulane_89652 |
| Date | January 2019 |
| Contributors | He, Ziyuan (author), Kuroda, Marcelo (Thesis advisor), School of Medicine Biomedical Sciences Graduate Program (Degree granting institution) |
| Publisher | Tulane University |
| Source Sets | Tulane University |
| Language | English |
| Detected Language | English |
| Type | Text |
| Format | electronic, pages: 111 |
| Rights | No embargo, Copyright is in accordance with U.S. Copyright law. |
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