Neuroscience Research Laboratory, Department of Neurology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
PLoS One. 2012;7(6):e38382. doi: 10.1371/journal.pone.0038382. Epub 2012 Jun 7.
We earlier reported elevated chemokine ligand-2 (CCL2) in Indian amyotrophic lateral sclerosis (ALS) patients. We now analysed chemokine receptor-2 (CCR2), the receptor of CCL2, in these ALS patients.
Indian sporadic ALS patients (n=50) were included on the basis of El Escorial criteria. Percentage (%) of CCR2 expressing peripheral blood mononuclear cells (PBMCs) was evaluated using Flow Cytometry. Real Time Polymerase Chain Reaction (PCR) was used to quantitate CCR2 mRNA expression in PBMCs. Normal controls (n = 40) were also included for comparison.
Flow Cytometry revealed significantly reduced CCR2 expressing PBMCs in the ALS patients. We also found a significant decline in number of CCR2 expressing PBMCs in limb onset ALS when compared to bulbar onset ALS. PBMCs from ALS patients showed substantial down-regulation of CCR2 mRNA. CCR2 mRNA expression was found to be decreased among limb ALS patients as compared to bulbar onset ALS. Further, the count of CCR2+ PBMCs and CCR2 mRNA transcript in PBMCs was significantly lower in severe and moderate ALS as compared to ALS patients with mild impairments.
Downregulation of PBMCs CCR2 may indicate its etio-pathological relevance in ALS pathogenesis. Reduced PBMCs CCR2 may result in decreased infiltration of leukocytes at the site of degeneration as a compensatory response to ALS. CCR2 levels measurements in hematopoietic stem cells and estimation of comparative PBMCs count among ALS, disease controls and normal controls can unveil its direct neuroprotective role. However, the conclusions are restricted by the absence of neurological/non-neurological disease controls in the study.
我们之前报道了印度肌萎缩侧索硬化症（ALS）患者趋化因子配体-2（CCL2）水平升高。我们现在分析了这些 ALS 患者趋化因子受体-2（CCR2），即 CCL2 的受体。
根据埃尔埃斯科里亚尔标准纳入印度散发性 ALS 患者（n=50）。使用流式细胞术评估 CCR2 表达外周血单核细胞（PBMC）的百分比（%）。使用实时聚合酶链反应（PCR）定量 PBMC 中的 CCR2 mRNA 表达。还纳入了 40 名正常对照者进行比较。
流式细胞术显示 ALS 患者的 CCR2 表达 PBMC 明显减少。我们还发现，与延髓发病 ALS 相比，肢体发病 ALS 中 CCR2 表达 PBMC 的数量明显下降。ALS 患者的 PBMC 显示 CCR2 mRNA 表达明显下调。与延髓发病 ALS 相比，肢体发病 ALS 患者的 CCR2 mRNA 表达降低。此外，与轻度受损的 ALS 患者相比，严重和中度 ALS 患者的 CCR2+PBMCs 和 PBMCs CCR2 mRNA 转录物的计数明显降低。
PBMCs CCR2 的下调可能表明其在 ALS 发病机制中的病因发病学相关性。PBMCs CCR2 的减少可能导致退化部位白细胞浸润减少，作为对 ALS 的代偿反应。在造血干细胞中测量 CCR2 水平，并在 ALS、疾病对照和正常对照者中估计比较 PBMCs 计数，可以揭示其直接的神经保护作用。然而，由于研究中缺乏神经/非神经疾病对照者，因此结论受到限制。
