The levels of chemokines CXCL8, CCL2 and CCL5 in multiple sclerosis patients are linked to the activity of the disease

Bartosik-Psujek, Halina; Stelmasiak, Z

doi:10.1111/j.1468-1331.2004.00951.x

Cited by 91 publications

(64 citation statements)

References 22 publications

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“…Results of such studies can have therapeutic implications, as receptors that facilitate leukocyte transmigration can be modulated systemically without recourse to agents capable of crossing the BBB. Previous studies in our laboratory supported the hypothesis that CCL2-CCR2 interactions are important for mononuclear cell migration across the BBB (despite low levels of CCL2 and CCR2+ cells in the CSF and brain parenchyma in MS respectively [24,[26][27][28]). We also showed that CXCR3 was a marker of CD4+ memory T-lymphocytes capable of migrating across the BBB in vitro, without playing an active role in transmigration [25].…”

Section: Introductionsupporting

confidence: 59%

“…Previous work in our laboratory has shown that CCR2 might be important for the early transmigration of receptorpositive monocytes and T-cells through the IVBBB, with CCL2 consumption by migrating mononuclear cells occurring in conjunction with receptor down-regulation in vitro [24]. This work provides an explanation for the reduced mononuclear cell CCR2 surface expression in MS lesions and reduced CSF CCL2 levels in MS patients during active disease [26][27][28]. We have also shown that CXCR3 is a surface marker for CD4+ T-cells capable of undergoing transmigration in vitro and have postulated that it does not play an active role in T-cell transmigration in vivo, despite being present on virtually all perivascular CD4+ T-cells in MS, as collaborated by observations in EAE using CXCR3 knockout mice [25,31,39,44].…”

Section: Discussionmentioning

confidence: 74%

“…A mean of 22% (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) of the input CD3+ T-cells expressed CCR5. There was no change in the total numbers of CD3+CCR5+ T-cells in either the basal IVBBB or aIVBBB assays, comparing the mean number of input CD3+CCR5+ T cells with the mean total numbers of non-migrating and migrating CD3+CCR5+ T-cells in the absence of CCL5 (Table 2a).…”

Section: Regulation Of Ccr5 On Migrating Cd3+ T Cells In the Absence mentioning

confidence: 99%

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CCR5 expression on monocytes and T cells: Modulation by transmigration across the blood–brain barrier in vitro

Ubogu

Callahan

Tucky

et al. 2006

Cellular Immunology

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Observational studies in multiple sclerosis (MS) demonstrated altered expression of chemokine receptors (CkRs) on comparable populations of mononuclear cells (e.g. CD4 + /CD45RO + T-cells) in brain sections compared with blood. These findings raised questions about the regulation of CkRs on trafficking cells. Regulatory processes for CkRs are complex: examples include down-regulation following ligand engagement during migration and either up-or down-regulation following activation. Additionally, CkRs that mediate transmigration without being down-regulated will be selectively enriched on migrating cells in the inflammatory site. Finally, CkRs may act as functionally neutral markers of activated cells capable of undergoing transmigration. Clarifying CkR regulation may aid in the selection and application of antagonists for treating neuroinflammation. Mechanisms of receptor regulation during transmigration cannot be studied by descriptive methods. We evaluated CCR5 expression on CD14+ monocytes and CD3+ T-cells following CCL5-driven transmigration through an in vitro blood-brain barrier (IVBBB), as both T-cells and monocytes in MS lesions express CCR5. CCR5 expression was augmented on non-migrating CD14+ but not CD3+ cells, suggesting selective activation of monocytes by incubation in contact with endothelial cells. As proposed from observational studies, CCR5 was enriched on monocytes that migrated spontaneously in the absence of exogenous chemokine. Addition of the CCR5 ligand CCL5 to the lower chamber led to enhanced CD3+ T-cell migration. Interestingly, CCR5 was down-regulated on both CD14+ monocytes and CD3+ T cells during CCL5-driven migration. These results are distinct from those obtained in comparable studies of CCR2 and CXCR3, suggesting that the specifics for CkR expression should be studied for individual receptors on each leukocyte subpopulation during the design of strategies for pharmacological blockade in neuroinflammation.

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Section: Introductionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 74%

Section: Regulation Of Ccr5 On Migrating Cd3+ T Cells In the Absence mentioning

confidence: 99%

See 1 more Smart Citation

CCR5 expression on monocytes and T cells: Modulation by transmigration across the blood–brain barrier in vitro

Ubogu

Callahan

Tucky

et al. 2006

Cellular Immunology

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“…There are discordant results in the literature concerning CSF CCL5 levels in MS. Some studies failed to find any difference among groups (14,15), while others demonstrated increased CSF levels of CCL5 during MS relapses (10,22,23). The fact that the CSF concentration of this chemokine is very low and near the lower limit of detection by ELISA may explain these discrepant results.…”

Section: Discussionmentioning

confidence: 99%

Chemokines in the cerebrospinal fluid of patients with active and stable relapsing-remitting multiple sclerosis

Moreira

Souza

Lana-Peixoto

et al. 2006

Braz J Med Biol Res

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Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the human central nervous system. Although its etiology is unknown, the accumulation and activation of mononuclear cells in the central nervous system are crucial to its pathogenesis. Chemokines have been proposed to play a major role in the recruitment and activation of leukocytes in inflammatory sites. They are divided into subfamilies on the basis of the location of conserved cysteine residues. We determined the levels of some CC and CXC chemokines in the cerebrospinal fluid (CSF) of 23 relapsing-remitting MS patients under interferon-ß-1a therapy and 16 control subjects using ELISA. MS patients were categorized as having active or stable disease. CXCL10 was significantly increased in the CSF of active MS patients (mean ± SEM, 369.5 ± 69.3 pg/mL) when compared with controls (178.5 ± 29.1 pg/mL, P < 0.05). CSF levels of CCL2 were significantly lower in active MS (144.7 ± 14.4 pg/mL) than in controls (237.1 ± 16.4 pg/ mL, P < 0.01). There was no difference in the concentration of CCL2 and CXCL10 between patients with stable MS and controls. CCL5 was not detectable in the CSF of most patients or controls. The qualitative and quantitative differences of chemokines in CSF during relapses of MS suggest that they may be useful as a marker of disease activity and of the mechanisms involved in the pathogenesis of the disease. Correspondence

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“…Patients with MS have elevated percentages of CCR5 expressing blood T cells compared with healthy controls (64). Significantly higher levels of CCL5 and CCL3 were found in the CSF of patients with MS in relapses (65)(66)(67). It was suggested that the CCR5 receptor plays a major role in the recruitment of T cells in MS (52,68).…”

Section: Chemokines and Chemokine Receptors In Msmentioning

confidence: 99%

Chemokines and chemokine receptors in multiple sclerosis. Potential targets for new therapies

2007

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Multiple sclerosis (MS) is a chronic demyelinating disease of the human central nervous system of a still unknown etiology. The autoimmune inflammatory process is believed to be essential for the development of the disease. Several different studies have shown that chemokines and chemokine receptors are involved in the pathogenesis of MS. Chemokines can mediate the trafficking of immune cells across the blood-brain barrier, and regulate their transfer to lesion sites. Chemokines were detected in actively demyelinating lesions and were found to be elevated in the cerebrospinal fluid of patients with MS during relapse. Different pairs of chemokine receptors and their ligands seem to play a pathogenic role in MS (e.g., CXCR3 and CXCL9, CXCL10; CCR1 and CCL3, CCL4, CCL5; CCR2 and CCL2; CCR5 and CCL3, CCL4, CCL5). Interfering with the chemokine system may be an effective therapeutic approach in MS. In this review we briefly summarize the results of the previous studies and identify the most important findings in the field.

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The levels of chemokines CXCL8, CCL2 and CCL5 in multiple sclerosis patients are linked to the activity of the disease

Cited by 91 publications

References 22 publications

CCR5 expression on monocytes and T cells: Modulation by transmigration across the blood–brain barrier in vitro

CCR5 expression on monocytes and T cells: Modulation by transmigration across the blood–brain barrier in vitro

Chemokines in the cerebrospinal fluid of patients with active and stable relapsing-remitting multiple sclerosis

Chemokines and chemokine receptors in multiple sclerosis. Potential targets for new therapies

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