Astrocyte cultures from human embryonic brain: Characterization and modulation of surface molecules by inflammatory cytokines

F. Aloisi, G. Borsellino, P. Samoggia, U. Testa, C. Chelucci, G. Russo, C. Peschle, G. Levi

Research output: Contribution to journalArticle

Abstract

Astrocyte-enriched cultures were established upon passaging of primary cultures from the myelencephalon and mesencephalon of 7-9-week-old human embryos. Immunocytochemical analysis showed that third-fourth passage cultures were composed of a highly enriched population of proliferating, epithelioid cells, up to 90% of which expressed glial fibrillary acidic protein (GFAP); no macrophages and very few fibroblasts (+ astrocytes were obtained from each embryo and could be stored frozen and recultured. Using flow cytometric analysis, human astrocyte cultures were examined for basal and cytokine [interferon-γ (IFN-γ), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α)]-induced expression of molecules that may be involved in astrocyte-T-lymphocyte interactions. Cultured human astrocytes spontaneously expressed major histocompatibility complex (MHC) class I antigens and variable levels of MHC class II; MHC class I levels were increased upon IFN-γ and TNF-α treatment, whereas MHC class II antigens were induced on most of the astrocytes by IFN-γ. Among the molecules involved in antigen-independent interactions between T lymphocytes and target cells, lymphocyte function-associated molecule-3 (LFA-3) was spontaneously expressed by most cultured human astrocytes, whereas intercellular adhesion molecule-1 (ICAM-1) was present at variable levels in non-stimulated astrocytes and was greatly induced by IFN-γ, TNF-α, and IL-1β. In this study we also show that the above cytokines upregulate astroglial expression of adhesion molecules of the integrin family (VLA-1, VLA-2, and VLA-6) that may be involved in astrocyte-extracellular matrix interaction and play a role in the astrocyte reactive changes occurring at sites of brain injury and inflammation. The human astrocyte cultures developed here represent a useful in vitro model to further investigate mechanisms involved in bidirectional communication between central glia and cells of the immune system.

Original languageEnglish
Pages (from-to)494-506
Number of pages13
JournalJournal of Neuroscience Research
Volume32
Issue number4
Publication statusPublished - 1992

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Keywords

  • adhesion molecules
  • cytokine regulation
  • human astrocytes
  • major histocompatibility complex

ASJC Scopus subject areas

  • Neuroscience(all)

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