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蛋白质-能量营养不良小鼠在脂多糖诱导的内毒素血症后血液学反应及白细胞介素-1β产生的损伤

Impairment of the hematological response and interleukin-1β production in protein-energy malnourished mice after endotoxemia with lipopolysaccharide.

作者信息

Fock R A, Vinolo M A R, Blatt S L, Borelli P

机构信息

Laboratório de Hematologia Experimental, Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, SP, Brasil.

出版信息

Braz J Med Biol Res. 2012 Dec;45(12):1163-71. doi: 10.1590/s0100-879x2012007500151. Epub 2012 Sep 18.

Abstract

The objectives of this study were to determine if protein-energy malnutrition (PEM) could affect the hematologic response to lipopolysaccharide (LPS), the interleukin-1β (IL-1β) production, leukocyte migration, and blood leukocyte expression of CD11a/CD18. Two-month-old male Swiss mice were submitted to PEM (N = 30) with a low-protein diet (14 days) containing 4% protein, compared to 20% protein in the control group (N = 30). The total cellularity of blood, bone marrow, spleen, and bronchoalveolar lavage evaluated after the LPS stimulus indicated reduced number of total cells in all compartments studied and different kinetics of migration in malnourished animals. The in vitro migration assay showed reduced capacity of migration after the LPS stimulus in malnourished animals (45.7 ± 17.2 x 10(4) cells/mL) compared to control (69.6 ± 7.1 x 10(4) cells/mL, P ≤ 0.05), but there was no difference in CD11a/CD18 expression on the surface of blood leukocytes. In addition, the production of IL-1β in vivo after the LPS stimulus (180.7 pg·h-1·mL-1), and in vitro by bone marrow and spleen cells (41.6 ± 15.0 and 8.3 ± 4.0 pg/mL) was significantly lower in malnourished animals compared to control (591.1 pg·h-1·mL-1, 67.0 ± 23.0 and 17.5 ± 8.0 pg/mL, respectively, P ≤ 0.05). The reduced expression of IL-1β, together with the lower number of leukocytes in the central and peripheral compartments, different leukocyte kinetics, and reduced leukocyte migration capacity are factors that interfere with the capacity to mount an adequate immune response, being partly responsible for the immunodeficiency observed in PEM.

摘要

本研究的目的是确定蛋白质 - 能量营养不良(PEM)是否会影响对脂多糖(LPS)的血液学反应、白细胞介素 - 1β(IL - 1β)的产生、白细胞迁移以及血液白细胞CD11a/CD18的表达。将2月龄雄性瑞士小鼠分为PEM组(N = 30),给予低蛋白饮食(14天),蛋白质含量为4%,对照组(N = 30)蛋白质含量为20%。LPS刺激后评估血液、骨髓、脾脏和支气管肺泡灌洗的总细胞数,结果表明,在所有研究的隔室中,营养不良动物的总细胞数减少,且迁移动力学不同。体外迁移试验显示,与对照组(69.6 ± 7.1×10⁴个细胞/mL,P≤0.05)相比,LPS刺激后营养不良动物的迁移能力降低(45.7 ± 17.2×10⁴个细胞/mL),但血液白细胞表面CD11a/CD18的表达没有差异。此外,与对照组(分别为591.1 pg·h⁻¹·mL⁻¹、67.0 ± 23.0和17.5 ± 8.0 pg/mL,P≤0.05)相比,LPS刺激后营养不良动物体内IL - 1β的产生(180.7 pg·h⁻¹·mL⁻¹)以及骨髓和脾脏细胞体外产生的IL - 1β(41.6 ± 15.0和8.3 ± 4.0 pg/mL)显著降低。IL - 1β表达降低,以及中枢和外周隔室中白细胞数量减少、白细胞动力学不同和白细胞迁移能力降低,这些因素都会干扰产生充分免疫反应的能力,部分解释了PEM中观察到的免疫缺陷。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/339a/3854220/cb34b9ba964a/0100-879X-bjmbr-45-12-1163-gf01.jpg

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