Murine Astrocytes Express a Functional Chemokine Receptor

Abstract

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-1alpha (MIP-1alpha). Murine astrocytes demonstrate directed migration along a chemical gradient in response to 10(-10)-10(-8) M MIP-1alpha. Peak chemotactic responses are noted at 10(-9) M. MIP-1alpha-induced astrocyte migration is specifically inhibitable with pertussis toxin, suggesting a role for Galphai proteins in the signaling process. RT-PCR and in situ hybridization were used to identify expression of the murine CCR1 MIP-1alpha receptor on astrocytes. Astrocytes contain mRNA for CCR1, but messages for CCR4 and the orphan chemokine receptor MIP-1alphaR-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.

RANTES-mediated Chemokine Transcription in Astrocytes Involves Activation and Translocation of p90 Ribosomal S6 Protein Kinase (RSK)

“…The ability of RANTES to stimulate astrocytes is consistent with reports demonstrating that astrocytes express two independent high affinity RANTES receptors, CCR1 (41,42) and CCR5 (18,(43)(44)(45).…”

Absence of Macrophage-Inflammatory Protein-1α Delays Central Nervous System Demyelination in the Presence of an Intact Blood-Brain Barrier

“…The recruitment of astrocytes in response to chemokines is controversial because this cell type has long been thought of as a relatively nonmotile parenchymal cell (64). Astrocytes have been shown to migrate in vitro in response to chemokine gradients of KC, eotaxin, or MIP-1␣ (49,52,64). At 3.5 wk of cuprizone treatment, the number of astrocytes in the MIP-1␣ Ϫ/Ϫ mice was reduced when compared with wild-type mice (Fig.…”

Interferon-Independent, Human Immunodeficiency Virus Type 1 gp120-Mediated Induction of CXCL10/IP-10 Gene Expression by Astrocytes In Vivo and In Vitro

“…Thus, while astrocytes are unlikely to express CD4, the primary receptor for HIV-1 gp120 binding, other receptors probably serve this function. Possible candidates include the chemokine receptor CXCR4, which can serve as a coreceptor for HIV-1 gp120 (16,31) and is found on astrocytes (30,47,63). Such alternative HIV gp120 binding sites may prove to be pathophysiologically significant, since recent studies indicate that astrocytes can host nonproductive HIV-1 infection in vitro and in vivo (9).…”