Central nervous system chemokine mRNA accumulation follows initial leukocyte entry at the onset of acute murine experimental autoimmune encephalomyelitis.
Central nervous system (CNS) expression of two chemokine mRNAs, encoding monocyte chemoattractant protein-1 (MCP-1) and IFN-gamma-inducible protein (IP-10), was previously shown to be closely related to the onset of clinical signs of murine experimental autoimmune encephalomyelitis (EAE). Chemokine mRNAs accumulated in a striking, transient burst within astrocytes, near inflammatory leukocyte infiltrates. It remained unclear if chemokines functioned to initiate leukocyte entry into CNS tissues, or to amplify the intrathecal inflammatory reaction. To address this issue, we determined the expression of chemokine mRNAs at the earliest evidence of CNS immune-mediated inflammation. For these experiments, mice were sacrificed in pairs at varying times after immunization. Only one member of each pair was symptomatic for EAE at the time of sacrifice. Symptom presence correlated well with histological inflammation at the time of sacrifice. RNA was prepared from two CNS sites, brain and spinal cord, and expression of chemokine mRNAs was analyzed by a sensitive and quantitative reverse transcriptase/polymerase chain reaction dot-blot hybridization assay. CNS expressions of MCP-1 and IP-10 gene were correlated tightly with histological inflammation; indeed, chemokine expression was never detected in the absence of leukocyte infiltrates. In situ hybridizations showed that astrocytes expressed chemokine transcripts. These findings provide new information about mechanisms controlling chemokine mRNA expression during immune-mediated inflammation in EAE and are consistent with a role for chemokines as amplifiers of CNS inflammatory reactions.
Research Institute, Cleveland Clinic Foundation, Ohio 44195, USA.
A R
AR
Glabinski
M
M
Tani
V K
VK
Tuohy
R J
RJ
Tuthill
R M
RM
Ransohoff
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001327:Autoimmune Diseases / Q000235:genetics*; D001483:Base Sequence; D002490:Central Nervous System / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D008099:Liver / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis*
D018932:Chemokine CCL2; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D016207:Cytokines; D012333:RNA, Messenger