蛋白质-能量营养不良模型中骨髓淋巴细胞亚群的研究。

Study of lymphocyte subpopulations in bone marrow in a model of protein-energy malnutrition.

机构信息

Experimental Hematology Laboratory, Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, São Paulo University, São Paulo, Brazil.

出版信息

Nutrition. 2010 Oct;26(10):1021-8. doi: 10.1016/j.nut.2009.08.026. Epub 2009 Dec 29.

Abstract

OBJECTIVE

Protein-energy malnutrition (PEM) is an important public health problem affecting millions of people worldwide. Hematopoietic tissue requires a high nutrient supply, and a reduction in leukocytes, especially lymphocytes, suggests that some nutritional deficiencies might be altering bone marrow function and decreasing its ability to produce lymphocytes. In this study, we evaluated the effect that PEM has on lymphocyte subtypes and the cell cycle of CD5(+) cells.

METHODS

Swiss mice were subjected to PEM using a low-protein diet containing 4% protein. When the experimental group had lost about 20% of their original body weight, we collected blood and bone marrow cells and evaluated the hemogram, the myelogram, bone marrow lymphoid markers using flow cytometry, and the cell cycle in CD5(+) bone marrow.

RESULTS

Malnourished animals presented anemia, reticulocytopenia, and leukopenia with lymphopenia. The bone marrow was hypocellular, and flow cytometric analyses of bone marrow cells showed cells that were CD45(+) (91.2%), CD2(+) (84.9%), CD5(+) (37.3%), CD3(+) (23.5%), CD19(+) (43.3%), CD22(+) (34.7%), CD19(+)/CD2(+) (51.2%), CD19(+)/CD3(+) (24.0%), CD19(+)/CD5(+) (13.2%), CD22(+)/CD2(+) (40.1%), CD22(+)/CD3(+) (30.3%), and CD22(+)/CD5(+) (1.1%) in malnourished animals and CD45(+) (97.5%), CD2(+) (42.9%), CD5(+) (91.5%), CD3(+) (92.0%), CD19(+) (52.0%), CD22(+) (75.6%), CD19(+)/CD2(+) (62.0%), CD19(+)/CD3(+) (55.4%), CD19(+)/CD5(+) (6.7%), CD22(+)/CD2(+) (70.3%), CD22(+)/CD3(+) (55.9%), and CD22(+)/CD5(+) (8.4%) in control animals. Malnourished animals also presented more CD5(+) cells in the G0 phase of cell cycle development.

CONCLUSION

Malnourished animals presented bone marrow hypoplasia, maturation interruption, prominent lymphopenia with depletion in the lymphoid lineage, and changes in cellular development. We suggest that these changes are some of the primary causes of lymphopenia in cases of PEM and partly explain the increase in susceptibility to infections found in malnourished individuals.

摘要

目的

蛋白质能量营养不良(PEM)是影响全球数百万人的重要公共卫生问题。造血组织需要高营养供应,白细胞减少,特别是淋巴细胞减少,表明某些营养缺乏可能正在改变骨髓功能并降低其产生淋巴细胞的能力。在这项研究中,我们评估了 PEM 对淋巴细胞亚型和 CD5(+)细胞细胞周期的影响。

方法

使用含有 4%蛋白质的低蛋白饮食使瑞士小鼠发生 PEM。当实验组失去约 20%的初始体重时,我们收集血液和骨髓细胞,并使用流式细胞术评估血液常规、骨髓象、骨髓淋巴标记物,以及 CD5(+)骨髓中的细胞周期。

结果

营养不良的动物表现出贫血、网织红细胞减少和白细胞减少伴淋巴细胞减少。骨髓细胞减少,骨髓细胞的流式细胞分析显示 CD45(+)(91.2%)、CD2(+)(84.9%)、CD5(+)(37.3%)、CD3(+)(23.5%)、CD19(+)(43.3%)、CD22(+)(34.7%)、CD19(+)/CD2(+)(51.2%)、CD19(+)/CD3(+)(24.0%)、CD19(+)/CD5(+)(13.2%)、CD22(+)/CD2(+)(40.1%)、CD22(+)/CD3(+)(30.3%)和 CD22(+)/CD5(+)(1.1%)在营养不良的动物中,CD45(+)(97.5%)、CD2(+)(42.9%)、CD5(+)(91.5%)、CD3(+)(92.0%)、CD19(+)(52.0%)、CD22(+)(75.6%)、CD19(+)/CD2(+)(62.0%)、CD19(+)/CD3(+)(55.4%)、CD19(+)/CD5(+)(6.7%)、CD22(+)/CD2(+)(70.3%)、CD22(+)/CD3(+)(55.9%)和 CD22(+)/CD5(+)(8.4%)在对照动物中。营养不良的动物还表现出更多的 CD5(+)细胞处于细胞周期发育的 G0 期。

结论

营养不良的动物表现出骨髓发育不良、成熟中断、突出的淋巴细胞减少伴淋巴细胞谱系耗竭,以及细胞发育的变化。我们认为这些变化是 PEM 中淋巴细胞减少的一些主要原因,并部分解释了营养不良个体易感染的增加。

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