PMID- 11037977 OWN - NLM STAT- MEDLINE DCOM- 20001103 LR - 20061115 IS - 0741-5400 (Print) IS - 0741-5400 (Linking) VI - 68 IP - 4 DP - 2000 Oct TI - Monocyte:astrocyte interactions regulate MCP-1 expression in both cell types. PG - 545-52 AB - 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. FAU - Andjelkovic, A V AU - Andjelkovic AV AD - Department of Pharmacology, University of Connecticut Health Center, Farmington 06030, USA. FAU - Kerkovich, D AU - Kerkovich D FAU - Pachter, J S AU - Pachter JS LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - J Leukoc Biol JT - Journal of leukocyte biology JID - 8405628 RN - 0 (Chemokine CCL2) RN - 0 (Interleukin-1) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Vascular Cell Adhesion Molecule-1) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) SB - IM MH - Astrocytes/*cytology/metabolism/ultrastructure MH - Cell Adhesion MH - *Cell Communication MH - Cells, Cultured MH - Chemokine CCL2/*biosynthesis/genetics MH - Coculture Techniques MH - Gene Expression Regulation/*physiology MH - Humans MH - Intercellular Adhesion Molecule-1/physiology MH - Interleukin-1/physiology MH - Monocytes/*cytology/metabolism MH - Tumor Necrosis Factor-alpha/physiology MH - Vascular Cell Adhesion Molecule-1/physiology EDAT- 2000/10/19 11:00 MHDA- 2001/02/28 10:01 CRDT- 2000/10/19 11:00 PHST- 2000/10/19 11:00 [pubmed] PHST- 2001/02/28 10:01 [medline] PHST- 2000/10/19 11:00 [entrez] PST - ppublish SO - J Leukoc Biol. 2000 Oct;68(4):545-52.