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Volume 17, Number 17, Issue of September 1, 1997 pp. 6522-6528
Copyright ©1997 Society for Neuroscience

Murine Astrocytes Express a Functional Chemokine Receptor

Received April 15, 1997; revised June 9, 1997; accepted June 11, 1997.

Shigeyuki Tanabe, Michael Heesen, Michael A. Berman, Michael B. Fischer, Izumi Yoshizawa, Yi Luo, and Martin E. Dorf

Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115

Elevated levels of chemokines have been observed in various diseases of the CNS. Little is known, however, about how these chemokines affect parenchymal cells of the CNS. The current studies examine astrocyte chemotaxis to the mouse chemokine macrophage inflammatory protein-1 (MIP-1). Murine astrocytes demonstrate directed migration along a chemical gradient in response to 10¹⁰-10⁸ M MIP-1. Peak chemotactic responses are noted at 10⁹ M. MIP-1-induced astrocyte migration is specifically inhibitable with pertussis toxin, suggesting a role for G_i proteins in the signaling process.

RT-PCR and in situ hybridization were used to identify expression of the murine CCR1 MIP-1 receptor on astrocytes. Astrocytes contain mRNA for CCR1, but messages for CCR4 and the orphan chemokine receptor MIP-1R-like#1 were not detected. The combined results suggest that a functional chemokine receptor is expressed on resident cells of the CNS. We speculate that the interactions of chemokines with astrocytes are involved in inflammatory reactions of the CNS.

Key words: astrocytes; chemokines; chemokine receptors; chemotaxis; inflammation; macrophage inflammatory protein-1; neuroimmunology

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