Monocyte activation in multiple sclerosis

Reder, Anthony T.; Genç, Kürşad; Byskosh, Paul V; Porrini, A.M.

doi:10.1177/135245859800400314

Cited by 34 publications

(15 citation statements)

References 50 publications

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“…Significant differences in full blood count parameters from the MS cohort were observed, and consistent with previous literature on female MS patients, ESR results were significantly increased compared to CFS/ME and non‐fatigued controls . This result suggests that there is significant peripheral inflammation in this cohort of untreated patients with MS. Additional significant increases were reported for lymphocyte and monocyte results in the MS cohort compared to CFS/ME and the non‐fatigued controls; however, previous literature has reported no significant differences . The small sample size may contribute to differences observed in white blood cell parameters in this MS cohort.…”

Section: Discussionmentioning

confidence: 56%

Pilot Study of Natural Killer Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis

et al. 2015

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Patients with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and multiple sclerosis (MS) suffer from debilitating fatigue which is not alleviated by rest. In addition to the fatigue-related symptoms suffered by patients with CFS/ME and MS, dysfunction of the immune system and, in particular, reduced natural killer (NK) cell cytotoxic activity has also been reported in CFS/ME and MS. The purpose of this pilot study was to compare NK cellular mechanisms in patients with CFS/ME and MS to investigate potential dysfunctions in the NK cell activity pathway. Flow cytometry protocols assessed CD56 dim CD16 + and CD56 bright CD16 +/À NK cell expression of adhesion molecules, NK activating and inhibiting receptors, NK cell maturation and lytic proteins. All participants in this study were female and included 14 patients with CFS/ME, nine patients with MS and 19 non-fatigued controls. The patient groups and the non-fatigued controls were not taking any immunosuppressive or immune-enhancing medications. In the MS cohort, KIR2DL5 was significantly increased on CD56 bright CD16 +/À NK cells and expression of CD94 was significantly increased on CD56 dim CD16 + NK cells in comparison with the controls. Co-expression of CD57 and perforin was significantly increased on CD56 dim CD16 + NK cells from patients with CFS/ME compared to the MS and non-fatigued control participants. The results from this pilot study suggest that NK cells from patients with CFS/ME and MS may have undergone increased differentiation in response to external stimuli which may affect different mechanisms in the NK cell cytotoxic activity pathway.

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Section: Discussionmentioning

confidence: 56%

Pilot Study of Natural Killer Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis

et al. 2015

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“…It therefore seems possible that decreased levels of IFNγ and IL-1β in spinal cord lesions in the NG2 null mouse (or altered activities of cells expressing these cytokines) are responsible for the reduced white matter damage seen in these mice. Moreover, decreased IL-4 production in the CNS exacerbates experimental autoimmune encephalitis, and is associated with increased infiltration of inflammatory cells [56], while increased IL-10 expression is associated with reduced inflammation [57]. The possibility that NG2 null macrophages/microglia may exhibit less inflammatory properties than wild type cells is in line with the in vitro finding of a reduced inflammatory phenotype upon knockdown of NG2 in microglia [58].…”

Section: Discussionmentioning

confidence: 99%

Reduced inflammation accompanies diminished myelin damage and repair in the NG2 null mouse spinal cord

Kuchárová

Chang

Böör

et al. 2011

J Neuroinflammation

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BackgroundMultiple sclerosis (MS) is a demyelinating disease in which blood-derived immune cells and activated microglia damage myelin in the central nervous system. While oligodendrocyte progenitor cells (OPCs) are essential for generating oligodendrocytes for myelin repair, other cell types also participate in the damage and repair processes. The NG2 proteoglycan is expressed by OPCs, pericytes, and macrophages/microglia. In this report we investigate the effects of NG2 on these cell types during spinal cord demyelination/remyelination.MethodsDemyelinated lesions were created by microinjecting 1% lysolecithin into the lumbar spinal cord. Following demyelination, NG2 expression patterns in wild type mice were studied via immunostaining. Immunolabeling was also used in wild type and NG2 null mice to compare the extent of myelin damage, the kinetics of myelin repair, and the respective responses of OPCs, pericytes, and macrophages/microglia. Cell proliferation was quantified by studies of BrdU incorporation, and cytokine expression levels were evaluated using qRT-PCR.ResultsThe initial volume of spinal cord demyelination in wild type mice is twice as large as in NG2 null mice. However, over the ensuing 5 weeks there is a 6-fold improvement in myelination in wild type mice, versus only a 2-fold improvement in NG2 null mice. NG2 ablation also results in reduced numbers of each of the three affected cell types. BrdU incorporation studies reveal that reduced cell proliferation is an important factor underlying NG2-dependent decreases in each of the three key cell populations. In addition, NG2 ablation reduces macrophage/microglial cell migration and shifts cytokine expression from a pro-inflammatory to anti-inflammatory phenotype.ConclusionsLoss of NG2 expression leads to decreased proliferation of OPCs, pericytes, and macrophages/microglia, reducing the abundance of all three cell types in demyelinated spinal cord lesions. As a result of these NG2-dependent changes, the course of demyelination and remyelination in NG2 null mice differs from that seen in wild type mice, with both myelin damage and repair being reduced in the NG2 null mouse. These studies identify NG2 as an important factor in regulating myelin processing, suggesting that therapeutic targeting of the proteoglycan might offer a means of manipulating cell behavior in demyelinating diseases.

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“…Monocytes are also involved but can play a dual role by promoting or resolving inflammation depending on their activation state 1 . Recent studies have shown that circulating monocytes in MS patients resemble classically activated monocytes, 2 , 3 , 4 and this classical activation state is found on both of the major monocyte subsets 3 …”

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confidence: 99%

Glatiramer acetate treatment normalized the monocyte activation profile in MS patients to that of healthy controls

et al. 2016

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Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system, and monocytes contribute to MS-associated neuroinflammation. While classically activated monocytes promote inflammation, type II-activated monocytes improve the course of MS. This study investigated type II activation of monocytes and their two main subsets, namely CD14 (CD14CD16 subset) and CD16 monocytes (CD14CD16 subset), by glatiramer acetate (GA) or intravenous immunoglobulin-associated immune complexes (IC), both of which are known MS treatments. Total monocytes and subsets were isolated from peripheral blood mononuclear cells (PBMC) of healthy controls, untreated MS patients (MS) and GA-treated MS patients (GA-MS). In contrast to the more activated ex vivo profile of monocytes from the MS group, monocytes from the GA-MS group resembled those from healthy controls. In vitro type II activation with GA primarily reduced CD40, CD86 and IL-12p40 whereas type II activation with IC consistently reduced CD40 but increased interleukin-10 (IL-10), suggesting that the GA and IC activation pathways are distinct. Moreover, while GA treatment reduced IL-12p40 by both CD14 and CD16 subsets, IC treatment only enhanced IL-10 by the CD16 subset. Further analysis of the CD16 subset revealed that MS patients had a greatly expanded CD14CD16 population while both CD14CD16 and CD14CD16 monocyte populations were expanded in GA-MS patients. Finally, a global analysis of the ex vivo monocyte data indicated that GA treatment distinctly altered the monocyte profile of MS patients, further supporting the idea that GA directly targets monocytes.

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Monocyte activation in multiple sclerosis

Cited by 34 publications

References 50 publications

Pilot Study of Natural Killer Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis

Pilot Study of Natural Killer Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis

Reduced inflammation accompanies diminished myelin damage and repair in the NG2 null mouse spinal cord

Glatiramer acetate treatment normalized the monocyte activation profile in MS patients to that of healthy controls

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