Monocyte chemoattractant protein-1 expression and macrophage infiltration in gliomas

Acta Neuropathol. 1997 May;93(5):518-27. doi: 10.1007/s004010050647.

Abstract

While the number of reports on macrophage infiltration of gliomas is increasing, the extent and mechanisms of macrophage recruitment remain unclear. To investigate whether monocyte chemoattractant protein-1 (MCP-1) plays a role in this process, in situ hybridisation (ISH) was performed for 22 glioblastomas (GBM), 1 anaplastic astrocytoma (AA) and 4 grade II fibrillary astrocytomas (AII) and reverse transcription-polymerase chain reaction was performed in 13 GBM, 1 AA and 3 AII. High levels of MCP-1 mRNA were detectable in most GBM, while a lower level was detected in AII. Many tumour-associated macrophages (TAM) could be demonstrated by immunohistochemistry (IHC) in most GBM, while the AII contained a lower number of TAM. The positive correlation between the MCP-1 level and abundance of TAM suggested that MCP-1 has a role in TAM recruitment. By combining ISH and IHC, high levels of MCP-1 mRNA were shown both in tumour cells and TAM. Along tumour borders, reactive astrocytes and microglia also expressed MCP-1. In areas with T lymphocyte infiltration, larger numbers of MCP-1-positive cells with an enhanced level of expression could be identified. We propose that the mechanism of macrophage recruitment is, at least partly, effected by constitutive expression and T cell-mediated up-regulation of MCP-1 in tumour cells and TAM. The production of MCP-1 by TAM establishes a positive amplification circuit for macrophage recruitment in gliomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Astrocytoma / metabolism
  • Astrocytoma / pathology
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology*
  • Chemokine CCL2 / biosynthesis*
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Glioma / metabolism*
  • Glioma / pathology*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Macrophages / physiology*
  • Polymerase Chain Reaction
  • RNA, Messenger / biosynthesis
  • T-Lymphocytes / physiology

Substances

  • Chemokine CCL2
  • RNA, Messenger