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老年个体髋部骨折后单核细胞表型和功能的改变:一项为期6个月的纵向研究。

Alterations in Monocyte Phenotypes and Functions after a Hip Fracture in Elderly Individuals: A 6-Month Longitudinal Study.

作者信息

Baëhl Sarra, Garneau Hugo, Lorrain Dominique, Viens Isabelle, Svotelis Amy, Lord Janet M, Cabana François, Larbi Anis, Dupuis Gilles, Fülöp Tamàs

机构信息

Division of Geriatrics and Research Center on Aging, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, Que., Canada.

出版信息

Gerontology. 2016;62(5):477-90. doi: 10.1159/000443142. Epub 2016 Jan 27.

Abstract

BACKGROUND

Healthy elderly individuals are particularly prone to catastrophic events at any moment of their lives. One stressful event for individuals aged 65 and older is a fall that results in a fracture of the hip (HF). HF causes a state of inflammation that may affect immune responses. In this connection, we have reported that HF induced alterations in neutrophil functions.

OBJECTIVE

To assess the impact of HF on classical (cM), intermediate (iM) and non-classical (ncM) monocyte subsets.

METHODS

Distribution, functions (chemotaxis, phagocytosis, superoxide production and cytokine production), phenotype and activation (NF-x03BA;B and PI3K) were evaluated in monocyte subsets before surgery and 6 weeks and 6 months after the event.

RESULTS

The distribution of cM and ncM was unchanged, but iM transiently increased before surgery. Sustained increases (iM response to CCL2 and CX3CL1) and decreases (cM and ncM response to CCL2) in chemotaxis were observed. Phagocytosis and superoxide production were impaired in cM but not in iM or ncM. Sustained expression of HLA-DR occurred in cM but not in iM and ncM. Sustained decreased expression of CD11b occurred only in ncM. Sustained decreases (cM and ncM) and increases (iM) in CCR2 expression were observed. An elevated expression of CX3CR1 was found only in iM. cM produced elevated quantities of TNFα. There was a transient oxidative burst of production before surgery in iM and a sustained decrease in ncM. IL-10 production was severely impaired in cM and decreased in iM prior to surgery. Sustained activation (cM), inhibition (ncM) and transient activation (iM) of NF-x03BA;B were observed. Activation of PI3K was severely impaired in cM and ncM but was sustained in iM.

CONCLUSION

HF had more impact on cM and ncM functions than on iM. HF triggered a switch in cM functions from phagocytic to inflammatory elevated TNFα-producing cells. These changes may impact clinical outcomes of HF with respect to inflammation, opportunistic infections and physical recovery.

摘要

背景

健康的老年人在其生命中的任何时刻都特别容易遭遇灾难性事件。对于65岁及以上的个体而言,一种压力事件是跌倒导致髋部骨折(HF)。髋部骨折会引发炎症状态,这可能会影响免疫反应。在此方面,我们已经报道过髋部骨折会引起中性粒细胞功能的改变。

目的

评估髋部骨折对经典(cM)、中间型(iM)和非经典(ncM)单核细胞亚群的影响。

方法

在手术前以及事件发生后的6周和6个月,对单核细胞亚群的分布、功能(趋化性、吞噬作用、超氧化物产生和细胞因子产生)、表型和活化(NF-κB和PI3K)进行评估。

结果

经典单核细胞和非经典单核细胞的分布未发生变化,但中间型单核细胞在手术前短暂增加。观察到趋化性持续增加(中间型单核细胞对CCL2和CX3CL1的反应)以及降低(经典单核细胞和非经典单核细胞对CCL2的反应)。经典单核细胞的吞噬作用和超氧化物产生受损,但中间型单核细胞和非经典单核细胞未受损。HLA-DR在经典单核细胞中持续表达,但在中间型单核细胞和非经典单核细胞中未表达。CD11b的持续表达降低仅在非经典单核细胞中出现。观察到CCR2表达持续降低(经典单核细胞和非经典单核细胞)以及增加(中间型单核细胞)。仅在中间型单核细胞中发现CX3CR1表达升高。经典单核细胞产生的TNFα量增加。中间型单核细胞在手术前有短暂的氧化爆发,而非经典单核细胞持续减少。白细胞介素-10的产生在经典单核细胞中严重受损,在手术前中间型单核细胞中减少。观察到NF-κB的持续活化(经典单核细胞)、抑制(非经典单核细胞)和短暂活化(中间型单核细胞)。PI3K的活化在经典单核细胞和非经典单核细胞中严重受损,但在中间型单核细胞中持续存在。

结论

髋部骨折对经典单核细胞和非经典单核细胞功能的影响大于对中间型单核细胞的影响。髋部骨折引发经典单核细胞功能从吞噬细胞转变为产生炎症性升高的TNFα的细胞。这些变化可能会影响髋部骨折在炎症、机会性感染和身体恢复方面的临床结果。

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