Expression of the β-chemokine receptors CCR2, CCR3 and CCR5 in multiple sclerosis central nervous system tissue

Simpson, Julie E.; Rezaie, Payam; Newcombe, Jia; Cuzner, M. L.; Male, David; Woodroofe, Nicola

doi:10.1016/s0165-5728(00)00274-5

Cited by 195 publications

(113 citation statements)

References 31 publications

Supporting

Mentioning

101

Contrasting

Unclassified

Order By: Relevance

“…It is also possible that pro-inflammatory cytokines and chemokines produced by astrocytes, microglia and early infiltrating leukocytes may activate infiltrating monocytes within the brain parenchyma, resulting in de novo CCR5 synthesis with subsequent increased surface expression on monocytes/macrophages. In addition, we also demonstrated enrichment of CD3+ CCR5+ T-cells on the abluminal side of the IVBBB in response to CCL5, consistent with observations in the perivascular spaces of MS lesions [36,37,39].…”

Section: Discussionsupporting

confidence: 89%

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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 89%

“…In addition, CCR5 is present on ~20% of circulating T-cells and as high as 90% of perivascular CD4+ T-cells in chronic active MS lesions [35][36][37][38][39]. To study CCR5 expression on mononuclear cells during BBB transmigration ex vivo, we utilized a well-established IVBBB model.…”

Section: Introductionmentioning

confidence: 99%

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

View full text Add to dashboard Cite

show abstract

“…Cells that express CCR2 in the CNS include macrophages/microglia, subpopulations of neurons and astrocytes (Simpson et al, 2000;Andjelkovic et al, 2002) and CCR2 expression is upregulated with inflammation (Banisadr et al, 2002;Mahad and Ransohoff, 2003).…”

Section: Discussionmentioning

confidence: 99%

CCR2 mediates increases in glial activation caused by exposure to HIV-1 Tat and opiates

El‐Hage

Ambati

et al. 2006

Journal of Neuroimmunology

View full text Add to dashboard Cite

To assess the role of CCL2/MCP-1 in opiate drug abuse and HIV-1 comorbidity, the effects of systemic morphine and intrastriatal HIV-1 Tat on macrophage/microglial and astroglial activation were assessed in wild type and CCR2 null mice. Tat and/or morphine additively increased the proportion of CCL2 immunoreactive astroglia. The effects of morphine were prevented by naltrexone. Glial activation was significantly reduced in CCR2(−/−) versus wild-type mice following Tat or morphine plus Tat exposure. Thus, CCR2 contributes to local glial activation caused by Tat alone or in the presence of opiates, implicating CCR2 signaling in HIV-1 neuropathogenesis in drug abusers and non-abusers.

show abstract

“…The CXC chemokine ligand 10 (CXCL10) is thought to play an important role in neuroinflammatory diseases and its action may involve neuronal cells (van Marle et al, 2004). During CNS neuroinflammation expression of CXCL10 is elevated several fold (Franciotta et al, 2001;Kieseier et al, 2002;Kolb et al, 1999;Letendre et al, 1999;Sorensen et al, 1999;Xia et al, 2000) and occurs in a variety of CNS cells including astrocytes, microglia, and neurons (Asensio and Campbell, 1999;Carter et al, 2007;Kutsch et al, 2000;Ransohoff et al, 1993;Rossi and Zlotnik, 2000;Shen et al, 2006;Simpson et al, 2000;Wang et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Chronic CXCL10 alters the level of activated ERK1/2 and transcriptional factors CREB and NF-κB in hippocampal neuronal cell culture

Bajova

Nelson

Gruol

2008

Journal of Neuroimmunology

View full text Add to dashboard Cite

Signal transduction pathways may be important targets of chemokines during neuroinflammation. In the current study, Western blot analyses show that in rat hippocampal neuronal/glial cell cultures chronic CXCL10 increases the level of protein for ERK1/2 as well as for the transcriptional factors CREB and NF-κB. Bcl-2, an anti-apoptotic protein whose expression can be regulated by a pathway involving ERK1/2, CREB and NF-κB, was also increased in the CXCL10 treated cultures. These results implicate a role for ERK1/2, CREB and NF-κB in effects of CXCL10 on hippocampal cells and suggest that chronic CXCL10 may have a protective role during certain neuroinflammatory conditions.

show abstract

Expression of the β-chemokine receptors CCR2, CCR3 and CCR5 in multiple sclerosis central nervous system tissue

Cited by 195 publications

References 31 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

CCR2 mediates increases in glial activation caused by exposure to HIV-1 Tat and opiates

Chronic CXCL10 alters the level of activated ERK1/2 and transcriptional factors CREB and NF-κB in hippocampal neuronal cell culture

Contact Info

Product

Resources

About