Mouse astrocytes respond to the chemokines MCP-1 and KC, but reverse transcriptase-polymerase chain reaction does not detect mRNA for the KC or new MCP-1 receptor.
Previous studies demonstrated the involvement of astrocytes in the development of astrogliosis, a condition in which these cells undergo proliferation and hypertrophy. To examine whether astrocytes could migrate into lesions, we tested the influence of the murine chemokines MCP-1, KC, TCA3, and MIP-1 beta on migration of cultured neonatal mouse astrocytes. Subnanomolar concentrations of MCP-1 and KC were active chemoattractants indicating that these molecules were effective at physiologic 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 protein-coupled receptors. To examine the receptors for these chemokines further, we cloned the mouse homolog of the human MCP-1 receptor from a mouse peritoneal exudate cell cDNA library. The gene had 78% nucleotide sequence homology with the human MCP-1 receptor (the nucleotide sequence of clone 1 encoding the mouse MCP-1 receptor can be obtained from the GenBank database, accession number U56819). However, reverse transcriptase-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.
Heesen
M
M
Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Tanabe
S
S
Berman
M A
MA
Yoshizawa
I
I
Luo
Y
Y
Kim
R J
RJ
Post
T W
TW
Gerard
C
C
Dorf
M E
ME
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D016466:CHO Cells / Q000187:drug effects / Q000276:immunology; D018932:Chemokine CCL2 / Q000235:genetics / Q000494:pharmacology*; D054360:Chemokine CXCL1; D018925:Chemokines; D019743:Chemokines, CXC; D002633:Chemotaxis / Q000187:drug effects* / Q000276:immunology; D003001:Cloning, Molecular; D006224:Cricetinae; D016207:Cytokines / Q000494:pharmacology*; D018076:DNA, Complementary / Q000235:genetics; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007223:Infant; D018836:Inflammation Mediators / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D037342:Pertussis Toxin; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000235:genetics*; D012680:Sensitivity and Specificity; D017386:Sequence Homology, Amino Acid; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
C515334:CCR2 protein, human; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D054360:Chemokine CXCL1; D018925:Chemokines; D019743:Chemokines, CXC; C475895:Cxcl1 protein, mouse; D016207:Cytokines; D018076:DNA, Complementary; D018836:Inflammation Mediators; D012333:RNA, Messenger; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D010566:Virulence Factors, Bordetella; C074302:keratinocyte-derived chemokines; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins