MCP-1, MCP-2 and MCP-3 expression in multiple sclerosis lesions: An immunohistochemical and in situ hybridization study

Carrie McManus, Joan W. Berman, Francesca M. Brett, Hugh Staunton, Michael Farrell, Celia F. Brosnan

Research output: Contribution to journalArticle

310 Citations (Scopus)

Abstract

Chemokines are low molecular weight chemotactic cytokines that have been shown to play a central role in the perivascular transmigration and accumulation of specific subsets of leukocytes at sites of tissue damage. Two major families have been defined depending on the positioning of four conserved cysteines. The CXC chemokines predominantly attract neutrophils, whereas the CC chemokines predominantly attract monocytes and other leukocyte cell types. Members of the monocyte chemotactic protein (MCP)-1 family form a major component of the CC family of chemokines and are considered the principal chemokines involved in the recruitment of monocytes/macrophages and activated lymphocytes. In this study we addressed the expression and distribution of MCP-1, -2 and -3 in multiple sclerosis (MS) lesions of differing ages and levels of inflammatory activity using immunohistochemistry and in situ hybridization. In acute and chronic-active MS lesions immunoreactivity for MCP-1, -2 and -3 was prominent throughout the lesion center with reactivity diminishing abruptly at the lesion edge. Hypertrophic astrocytes were strongly reactive and inflammatory cells showed variable reactivity. Outside of the lesion only hypertrophic astrocytes were reactive. The results obtained by in situ hybridization for MCP-1 were in agreement with those obtained by immunostaining. In more chronic lesions immunoreactivity for MCP-1, -2 and -3 was considerably diminished, and in chronic-silent lesions immunoreactivity was restricted to a few scattered reactive astrocytes. Normal control brains showed no immunoreactivity for MCP-1, -2 and -3. Although the cellular distribution of all three members of this family was similar, antibodies to MCP-3 gave prominent staining of the extracellular matrix that was not noted for MCP-1 and -2. These results support the conclusion that members of the MCP family of chemokines are involved in the development of MS lesions in the central nervous system.

Original languageEnglish (US)
Pages (from-to)20-29
Number of pages10
JournalJournal of Neuroimmunology
Volume86
Issue number1
DOIs
StatePublished - Jun 1 1998

Fingerprint

Chemokine CCL8
Chemokine CCL7
Chemokine CCL2
Multiple Sclerosis
In Situ Hybridization
Chemokines
Astrocytes
CC Chemokines
Monocytes
Monocyte Chemoattractant Proteins
Leukocytes
CXC Chemokines
Extracellular Matrix
Cysteine
Neutrophils
Central Nervous System
Molecular Weight
Immunohistochemistry
Macrophages
Lymphocytes

Keywords

  • Chemokine
  • Monocyte chemotactic protein-1 (MCP-1)
  • Multiple sclerosis (MS)

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology

Cite this

MCP-1, MCP-2 and MCP-3 expression in multiple sclerosis lesions : An immunohistochemical and in situ hybridization study. / McManus, Carrie; Berman, Joan W.; Brett, Francesca M.; Staunton, Hugh; Farrell, Michael; Brosnan, Celia F.

In: Journal of Neuroimmunology, Vol. 86, No. 1, 01.06.1998, p. 20-29.

Research output: Contribution to journalArticle

McManus, Carrie ; Berman, Joan W. ; Brett, Francesca M. ; Staunton, Hugh ; Farrell, Michael ; Brosnan, Celia F. / MCP-1, MCP-2 and MCP-3 expression in multiple sclerosis lesions : An immunohistochemical and in situ hybridization study. In: Journal of Neuroimmunology. 1998 ; Vol. 86, No. 1. pp. 20-29.
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AB - Chemokines are low molecular weight chemotactic cytokines that have been shown to play a central role in the perivascular transmigration and accumulation of specific subsets of leukocytes at sites of tissue damage. Two major families have been defined depending on the positioning of four conserved cysteines. The CXC chemokines predominantly attract neutrophils, whereas the CC chemokines predominantly attract monocytes and other leukocyte cell types. Members of the monocyte chemotactic protein (MCP)-1 family form a major component of the CC family of chemokines and are considered the principal chemokines involved in the recruitment of monocytes/macrophages and activated lymphocytes. In this study we addressed the expression and distribution of MCP-1, -2 and -3 in multiple sclerosis (MS) lesions of differing ages and levels of inflammatory activity using immunohistochemistry and in situ hybridization. In acute and chronic-active MS lesions immunoreactivity for MCP-1, -2 and -3 was prominent throughout the lesion center with reactivity diminishing abruptly at the lesion edge. Hypertrophic astrocytes were strongly reactive and inflammatory cells showed variable reactivity. Outside of the lesion only hypertrophic astrocytes were reactive. The results obtained by in situ hybridization for MCP-1 were in agreement with those obtained by immunostaining. In more chronic lesions immunoreactivity for MCP-1, -2 and -3 was considerably diminished, and in chronic-silent lesions immunoreactivity was restricted to a few scattered reactive astrocytes. Normal control brains showed no immunoreactivity for MCP-1, -2 and -3. Although the cellular distribution of all three members of this family was similar, antibodies to MCP-3 gave prominent staining of the extracellular matrix that was not noted for MCP-1 and -2. These results support the conclusion that members of the MCP family of chemokines are involved in the development of MS lesions in the central nervous system.

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