Identification of distinct monocyte phenotypes and correlation with circulating cytokine profiles in acute response to spinal cord injury: a pilot study.

Identification of distinct monocyte phenotypes and correlation with circulating cytokine profiles in acute response to spinal cord injury: a pilot study.
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DOI:
10.1016/j.pmrj.2013.10.006
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发表时间:
2014-04
期刊:
PM & R : the journal of injury, function, and rehabilitation
影响因子:
--
通讯作者:
Sowa G
Sowa G
中科院分区:
其他
文献类型:
--
作者:
Huang W;Vodovotz Y;Kusturiss MB;Barclay D;Greenwald K;Boninger ML;Coen PM;Brienza D;Sowa G

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在对创伤性脊髓损伤(SCI)的急性反应过程中,巨噬细胞浸润到损伤部位的情况并不均匀。巨噬细胞表型被表征为促炎性(M1)或抗炎性(M2)。动物研究表明,损伤部位的 M1/M2 优势与 SCI 后的自然恢复有关。旨在研究循环巨噬细胞前体单核细胞 (MO) 的表型是否在 SCI 急性期发生改变并与循环炎症细胞因子相对应。前瞻性观察队列研究。美国宾夕法尼亚州的一个学术医疗中心。 27 名完全或不完全创伤性 SCI 受试者在 SCI 损伤后 7 天内入组。使用流式细胞术在 SCI 后第一周内定义 MO 表型,并与历史未受伤对照进行比较。使用 Luminex 评估 SCI 后两周内连续血液样本中 25 种细胞因子/趋化因子的浓度。方差分析用于确定表型和细胞因子谱之间的相关性。患者亚群被确定为 M1 显性或 M2 显性循环 MO,与未受伤对照不同。 M1 主导型与较高循环水平的促炎介质 IL-12p70 和 IP-10 以及较低水平的抗炎细胞因子 IL-10、IL-15 和 IL-7 相关,而 M2 主导型则表现出相反的细胞因子谱,IL-10 和 IL-7 显着较高。在 SCI 后的急性期,在损伤严重程度相当的情况下,患者亚组表现出明显的 M1/M2 MO 优势,并且表型与 M1 或 M2 特异性细胞因子/趋化因子谱相关。尽管需要进一步研究来确定这些观察到的表型差异与功能恢复之间的关系,但我们的研究结果 1) 提供了第一个证据,表明对可比较的创伤性 SCI 的免疫反应可能存在个体差异,这对急性 SCI 的管理和康复具有潜在影响; 2)可能代表具有预后实用性的易于获取的生物标志物。
Macrophage infiltration to the injury site during the acute response to traumatic spinal cord injury (SCI) is not uniform. Macrophage phenotype has been characterized as either pro-inflammatory (M1) or anti-inflammatory (M2). Animal studies suggest that M1/M2 dominance at the site of injury relates to spontaneous recovery following SCI. To investigate whether the phenotype of circulating macrophage precursors-monocytes (MOs), is altered in the acute phase of SCI and corresponds to circulating inflammatory cytokines. Prospective observational cohort study. A single academic medical center in Pennsylvania, US. A cohort of 27 complete or incomplete traumatic SCI subjects enrolled within 7 days post-SCI injury. MO phenotype was defined within the first week post-SCI, using flow cytometry, and compared to historical uninjured controls. Concentrations of 25 cytokines/chemokines were assessed using Luminex in serial blood samples up to two weeks post-SCI. ANOVA was used to determine the correlations between the phenotypes and the cytokine profiles. Patients subsets were identified with either M1 dominant or M2 dominant circulating MOs distinct from the uninjured controls. The M1-dominant was associated with higher circulating levels of pro-inflammatory mediators IL-12p70 and IP-10, and lower levels of anti-inflammatory cytokines IL-10, IL-15 and IL-7, whereas the M2-dominant exhibited the opposite cytokine profiles with significantly higher IL-10 and IL-7. In the acute phase after SCI, at comparable injury severity, subgroups of patients exhibit distinct M1/M2 MOs dominance and the phenotype is correlated with M1 or M2-specific cytokine/chemokine profiles. Though further studies are needed to determine how these observed phenotypic differences relate to functional recovery, our findings 1) provide the first evidence indicating the possible individual differences in the immune responses to the comparable traumatic SCI, with potential implications for management of acute SCI and rehabilitation; 2) may represent easily accessible biomarkers with prognostic utility.
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