MOUSE ASTROCYTES RESPOND TO THE CHEMOKINES MCP-1 AND KC, BUT REVERSE-TRANSCRIPTASE POLYMERASE CHAIN-REACTION DOES NOT DETECT MESSENGER-RNA FOR THE KC OR NEW MCP-1 RECEPTOR

Previous studies demonstrated the involvement of astrocytes in the dev elopment of astrogliosis, a condition in which these cells undergo pro liferation and hypertrophy, To examine whether astrocytes could migrat e into lesions, we tested the influence of the murine chemokines MCP-1 , KC, TCA3, and MIP-1 beta on migration of cultured neonatal mouse ast rocytes. Subnanomolar concentrations of MCP-1 and KC were active chemo attractants indicating that these molecules were effective at physiolo gic concentrations. Specificity of MCP-1 was demonstrated by antibody inhibition and by the finding that the chemokine MIP-1 beta failed to induce astrocyte migration, The migratory responses were sensitive to pertussis toxin; this finding is consistent with involvement of G prot ein-coupled receptors, To examine the receptors for these chemokines f urther, we cloned the mouse homolog of the human MCP-1 receptor from a mouse peritoneal exudate cell cDNA library, The gene had 78% nucleoti de sequence homology with the human MCP-1 receptor (the nucleotide seq uence of clone 1 encoding the mouse MCP-1 receptor can be obtained fro m the GenBank database, accession number U56819), However, reverse tra nscriptase-polymerase chain reaction (RT-PCR) failed to detect message for either the MCP-1 or KC receptors in astrocytes. The combined data suggest that mouse astrocytes use novel receptors to recognize these chemokines. (C) 1996 Wiley-Liss, Inc.