Murine astrocytes express a functional chemokine receptor.
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.
Tanabe
S
S
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Heesen
M
M
Berman
M A
MA
Fischer
M B
MB
Yoshizawa
I
I
Luo
Y
Y
Dorf
M E
ME
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines / Q000378:metabolism*; D002633:Chemotaxis / Q000187:drug effects; D005260:Female; D015870:Gene Expression; D017403:In Situ Hybridization; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D037342:Pertussis Toxin; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines; D019402:Macrophage Inflammatory Proteins; D011956:Receptors, Cell Surface; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin