Monocyte : astrocyte interactions regulate MCP-1 expression in both cell types

As astrocytes are a source of monocyte chemoattractant protein-1 (MCP-1) an d lie in close apposition to brain microvessels, interactions between astro cytes and infiltrating monocytes might regulate production of this chemokin e, To investigate this possibility, a monocyte:astrocyte co-culture model w as utilized to assess the respective roles of these two cell types in regul ating MCP-1 production. Results indicate that, while neither monocytes nor astrocytes alone produce detectable levels of MCP-1, co-culture of these tw o 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- 1 beta) and tumor necrosis factor-alpha (TNF-alpha) are soluble mediators o f this response. These findings imply that monocyte extravasation into the CNS may be critically regulated at the blood-brain barrier by specialized m onocyte:astrocyte interactions.