Rapid Turnover and High Production Rate of Myeloid Cells in Adult Rhesus Macaques with Compensations during Aging

Rapid Turnover and High Production Rate of Myeloid Cells in Adult Rhesus Macaques with Compensations during Aging
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DOI:
10.4049/jimmunol.1800207
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发表时间:
2018-06-15
影响因子:
4.4
通讯作者:
Kuroda, Marcelo J.
Kuroda, Marcelo J.
中科院分区:
医学2区
文献类型:
--
作者:
He, Ziyuan;Allers, Carolina;Kuroda, Marcelo J.

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中性粒细胞、嗜碱性粒细胞和单核细胞通过骨髓生成在骨髓中持续产生,在血液中循环,并最终从循环中去除以维持体内平衡。为了定量稳态期间骨髓细胞运动的动力学,我们在健康恒河猴(Macaca mulatta)中应用5-溴-2 '-脱氧尿苷脉冲标记,然后进行血液学和流式细胞术分析。将结果应用于数学模型,并分别计算来自5-10岁猕猴的每种细胞类型的血液循环半衰期和每日产生的中性粒细胞(1.63 +/- 0.16 d,1.42 x 10(9)个细胞/l/d),嗜碱性粒细胞(1.78 +/- 0.30 d,5.89 x 10(6)个细胞/l/d)和CD 14(+)CD 16(-)经典单核细胞(1.01 +/- 0.15 d,3.09 x 10(8)个细胞/l/d)。经典单核细胞早在分裂后1天就被释放到血液循环中,而中性粒细胞在释放前4-5天仍留在骨髓中。在粒细胞中,中性粒细胞和嗜碱性粒细胞在骨髓成熟时间和血液循环中表现出不同的动力学。随着实际年龄的增加,中性粒细胞和嗜碱性粒细胞的日产量显着下降,但这些粒细胞的半衰期在3至19岁之间保持不变。相比之下,经典单核细胞的日产量在19岁时保持稳定,但半衰期显著下降。这些结果表明,相对较短的半衰期和持续补充中性粒细胞,嗜碱性粒细胞,和经典的单核细胞在稳态在成年恒河猴与补偿期间观察到的实际年龄增加。
Neutrophils, basophils, and monocytes are continuously produced in bone marrow via myelopoiesis, circulate in blood, and are eventually removed from circulation to maintain homeostasis. To quantitate the kinetics of myeloid cell movement during homeostasis, we applied 5-bromo-2'-deoxyuridine pulse labeling in healthy rhesus macaques (Macaca mulatta) followed by hematology and flow cytometry analyses. Results were applied to a mathematical model, and the blood circulating half-life and daily production, respectively, of each cell type from macaques aged 5-10 y old were calculated for neutrophils (1.63 +/- 0.16 d, 1.42 x 10(9) cells/l/d), basophils (1.78 +/- 0.30 d, 5.89 x 10(6) cells/l/d), and CD14(+)CD16(-) classical monocytes (1.01 +/- 0.15 d, 3.09 x 10(8) cells/l/d). Classical monocytes were released into the blood circulation as early as 1 d after dividing, whereas neutrophils remained in bone marrow 4-5 d before being released. Among granulocytes, neutrophils and basophils exhibited distinct kinetics in bone marrow maturation time and blood circulation. With increasing chronological age, there was a significant decrease in daily production of neutrophils and basophils, but the half-life of these granulocytes remained unchanged between 3 and 19 y of age. In contrast, daily production of classical monocytes remained stable through 19 y of age but exhibited a significant decline in half-life. These results demonstrated relatively short half-lives and continuous replenishment of neutrophils, basophils, and classical monocytes during homeostasis in adult rhesus macaques with compensations observed during increasing chronological age.