Discrepancy in CCL2 and CCR2 expression in white versus grey matter hippocampal lesions of Multiple Sclerosis patients

Marloes Prins, Ranjan Dutta, Bart Baselmans, John J P Brevé, John G J M Bol, Sadie A Deckard, Paul van der Valk, Sandra Amor, Bruce D Trapp, Helga E de Vries, Benjamin Drukarch, Anne-Marie van Dam

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

A remarkable pathological difference between grey matter lesions (GML) and white matter lesions (WML) in Multiple Sclerosis (MS) patients is the paucity of infiltrating leukocytes in GML. To better understand these pathological differences, we hypothesize that the chemokine monocyte chemotactic protein-1 (MCP-1 or CCL2), of importance for leukocyte migration, and its receptor CCR2 are more abundantly expressed in WML than in GML of MS patients. To this end, we analyzed CCL2 and CCR2 expression in the hippocampus, comprising WML and GML,of post-mortem MS patients, and of control subjects. CCL2 and CCR2 mRNA were significantly increased in demyelinated MS hippocampus. Semi-quantification of CCL2 and CCR2 immunoreactivity showed that CCL2 is present in astrocytes only in active WML. CCR2 is upregulated in monocytes/macrophages or amoeboid microglia in active WML, and in ramified microglia in active GML, although to a lesser extent. As a follow-up, we observed a significantly increased CCL2 production by WM-, but not GM-derived astrocytes upon stimulation with bz-ATP in vitro. Finally, upon CCL2 stimulation, GM-derived microglia significantly increased their proliferation rate. We conclude that within hippocampal lesions, CCL2 expression is mainly restricted to WML, whereas the receptor CCR2 is upregulated in both WML and GML. The relative absence of CCL2 in GML may explain the lack of infiltrating immune cells in this type of lesions. We propose that the divergent expression of CCL2 and CCR2 in WML and GML explains or contributes to the differences in WML and GML formation in MS.

Original languageEnglish
Pages (from-to)98
JournalActa Neuropathologica Communinications
Volume2
DOIs
Publication statusPublished - 23 Aug 2014

Cite this

@article{2663bb67f8464b0087f7a0ef58cb2a43,
title = "Discrepancy in CCL2 and CCR2 expression in white versus grey matter hippocampal lesions of Multiple Sclerosis patients",
abstract = "A remarkable pathological difference between grey matter lesions (GML) and white matter lesions (WML) in Multiple Sclerosis (MS) patients is the paucity of infiltrating leukocytes in GML. To better understand these pathological differences, we hypothesize that the chemokine monocyte chemotactic protein-1 (MCP-1 or CCL2), of importance for leukocyte migration, and its receptor CCR2 are more abundantly expressed in WML than in GML of MS patients. To this end, we analyzed CCL2 and CCR2 expression in the hippocampus, comprising WML and GML,of post-mortem MS patients, and of control subjects. CCL2 and CCR2 mRNA were significantly increased in demyelinated MS hippocampus. Semi-quantification of CCL2 and CCR2 immunoreactivity showed that CCL2 is present in astrocytes only in active WML. CCR2 is upregulated in monocytes/macrophages or amoeboid microglia in active WML, and in ramified microglia in active GML, although to a lesser extent. As a follow-up, we observed a significantly increased CCL2 production by WM-, but not GM-derived astrocytes upon stimulation with bz-ATP in vitro. Finally, upon CCL2 stimulation, GM-derived microglia significantly increased their proliferation rate. We conclude that within hippocampal lesions, CCL2 expression is mainly restricted to WML, whereas the receptor CCR2 is upregulated in both WML and GML. The relative absence of CCL2 in GML may explain the lack of infiltrating immune cells in this type of lesions. We propose that the divergent expression of CCL2 and CCR2 in WML and GML explains or contributes to the differences in WML and GML formation in MS.",
keywords = "Adenosine Triphosphate, Adult, Aged, Animals, Animals, Newborn, Bromodeoxyuridine, Cell Proliferation, Cells, Cultured, Chemokine CCL2, Female, Gene Expression, Gray Matter, Hippocampus, Histocompatibility Antigens Class II, Humans, Male, Middle Aged, Multiple Sclerosis, Myelin Basic Protein, Neuroglia, Platelet Aggregation Inhibitors, Rats, Rats, Wistar, Receptors, CCR2, White Matter, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't",
author = "Marloes Prins and Ranjan Dutta and Bart Baselmans and Brev{\'e}, {John J P} and Bol, {John G J M} and Deckard, {Sadie A} and {van der Valk}, Paul and Sandra Amor and Trapp, {Bruce D} and {de Vries}, {Helga E} and Benjamin Drukarch and {van Dam}, Anne-Marie",
year = "2014",
month = "8",
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doi = "10.1186/s40478-014-0098-6",
language = "English",
volume = "2",
pages = "98",
journal = "Acta Neuropathologica Communinications",
issn = "2051-5960",
publisher = "BioMed Central",

}

Discrepancy in CCL2 and CCR2 expression in white versus grey matter hippocampal lesions of Multiple Sclerosis patients. / Prins, Marloes; Dutta, Ranjan; Baselmans, Bart; Brevé, John J P; Bol, John G J M; Deckard, Sadie A; van der Valk, Paul; Amor, Sandra; Trapp, Bruce D; de Vries, Helga E; Drukarch, Benjamin; van Dam, Anne-Marie.

In: Acta Neuropathologica Communinications, Vol. 2, 23.08.2014, p. 98.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Discrepancy in CCL2 and CCR2 expression in white versus grey matter hippocampal lesions of Multiple Sclerosis patients

AU - Prins, Marloes

AU - Dutta, Ranjan

AU - Baselmans, Bart

AU - Brevé, John J P

AU - Bol, John G J M

AU - Deckard, Sadie A

AU - van der Valk, Paul

AU - Amor, Sandra

AU - Trapp, Bruce D

AU - de Vries, Helga E

AU - Drukarch, Benjamin

AU - van Dam, Anne-Marie

PY - 2014/8/23

Y1 - 2014/8/23

N2 - A remarkable pathological difference between grey matter lesions (GML) and white matter lesions (WML) in Multiple Sclerosis (MS) patients is the paucity of infiltrating leukocytes in GML. To better understand these pathological differences, we hypothesize that the chemokine monocyte chemotactic protein-1 (MCP-1 or CCL2), of importance for leukocyte migration, and its receptor CCR2 are more abundantly expressed in WML than in GML of MS patients. To this end, we analyzed CCL2 and CCR2 expression in the hippocampus, comprising WML and GML,of post-mortem MS patients, and of control subjects. CCL2 and CCR2 mRNA were significantly increased in demyelinated MS hippocampus. Semi-quantification of CCL2 and CCR2 immunoreactivity showed that CCL2 is present in astrocytes only in active WML. CCR2 is upregulated in monocytes/macrophages or amoeboid microglia in active WML, and in ramified microglia in active GML, although to a lesser extent. As a follow-up, we observed a significantly increased CCL2 production by WM-, but not GM-derived astrocytes upon stimulation with bz-ATP in vitro. Finally, upon CCL2 stimulation, GM-derived microglia significantly increased their proliferation rate. We conclude that within hippocampal lesions, CCL2 expression is mainly restricted to WML, whereas the receptor CCR2 is upregulated in both WML and GML. The relative absence of CCL2 in GML may explain the lack of infiltrating immune cells in this type of lesions. We propose that the divergent expression of CCL2 and CCR2 in WML and GML explains or contributes to the differences in WML and GML formation in MS.

AB - A remarkable pathological difference between grey matter lesions (GML) and white matter lesions (WML) in Multiple Sclerosis (MS) patients is the paucity of infiltrating leukocytes in GML. To better understand these pathological differences, we hypothesize that the chemokine monocyte chemotactic protein-1 (MCP-1 or CCL2), of importance for leukocyte migration, and its receptor CCR2 are more abundantly expressed in WML than in GML of MS patients. To this end, we analyzed CCL2 and CCR2 expression in the hippocampus, comprising WML and GML,of post-mortem MS patients, and of control subjects. CCL2 and CCR2 mRNA were significantly increased in demyelinated MS hippocampus. Semi-quantification of CCL2 and CCR2 immunoreactivity showed that CCL2 is present in astrocytes only in active WML. CCR2 is upregulated in monocytes/macrophages or amoeboid microglia in active WML, and in ramified microglia in active GML, although to a lesser extent. As a follow-up, we observed a significantly increased CCL2 production by WM-, but not GM-derived astrocytes upon stimulation with bz-ATP in vitro. Finally, upon CCL2 stimulation, GM-derived microglia significantly increased their proliferation rate. We conclude that within hippocampal lesions, CCL2 expression is mainly restricted to WML, whereas the receptor CCR2 is upregulated in both WML and GML. The relative absence of CCL2 in GML may explain the lack of infiltrating immune cells in this type of lesions. We propose that the divergent expression of CCL2 and CCR2 in WML and GML explains or contributes to the differences in WML and GML formation in MS.

KW - Adenosine Triphosphate

KW - Adult

KW - Aged

KW - Animals

KW - Animals, Newborn

KW - Bromodeoxyuridine

KW - Cell Proliferation

KW - Cells, Cultured

KW - Chemokine CCL2

KW - Female

KW - Gene Expression

KW - Gray Matter

KW - Hippocampus

KW - Histocompatibility Antigens Class II

KW - Humans

KW - Male

KW - Middle Aged

KW - Multiple Sclerosis

KW - Myelin Basic Protein

KW - Neuroglia

KW - Platelet Aggregation Inhibitors

KW - Rats

KW - Rats, Wistar

KW - Receptors, CCR2

KW - White Matter

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

U2 - 10.1186/s40478-014-0098-6

DO - 10.1186/s40478-014-0098-6

M3 - Article

VL - 2

SP - 98

JO - Acta Neuropathologica Communinications

JF - Acta Neuropathologica Communinications

SN - 2051-5960

ER -