Monocyte chemoattractant protein-1 expression and macrophage infiltration in gliomas

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.