* Blood-Brain Barrier Laboratory, Department of Pharmacology, University of Connecticut Health Center, Farmington, Connecticut
Correspondence: J. S. Pachter, Blood-Brain Barrier Laboratory, Department of Pharmacology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030. E-mail: PACHTER{at}SUN.UCHC.EDU
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-1ß) and tumor
necrosis factor-alpha (TNF-
) 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.
Key Words: blood-brain barrier • neuroinflammation • chemokines
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