Monocyte:astrocyte interactions regulate MCP-1 expression in both cell types.
As astrocytes are a source of monocyte chemoattractant protein-1 (MCP-1) and lie in close apposition to brain microvessels, interactions between astrocytes and infiltrating monocytes might regulate production of this chemokine. To investigate this possibility, a monocyte:astrocyte co-culture model was utilized to assess the respective roles of these two cell types in regulating MCP-1 production. Results indicate that, while neither monocytes nor astrocytes alone produce detectable levels of MCP-1, co-culture of these two cell types results in time-dependent production of this chemokine. Such production requires de novo protein synthesis and is dependent on physical contact between monocytes and astrocytes, involving engagement of the cell-adhesion molecules ICAM-1 and VCAM-1. Additionally, interleukin 1-beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) are soluble mediators of this response. These findings imply that monocyte extravasation into the CNS may be critically regulated at the blood-brain barrier by specialized monocyte:astrocyte interactions.
Andjelkovic
A V
AV
Department of Pharmacology, University of Connecticut Health Center, Farmington 06030, USA.
Kerkovich
D
D
Pachter
J S
JS
D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D002448:Cell Adhesion; D002450:Cell Communication; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D018920:Coculture Techniques; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D007375:Interleukin-1 / Q000502:physiology; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology
D018932:Chemokine CCL2; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1