Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients
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Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients. / Sørensen, Torben Lykke; Tani, M; Jensen, J; Pierce, V; Lucchinetti, C; Folcik, V A; Qin, Shuyuan; Rottman, J; Sellebjerg, F; Strieter, R M; Frederiksen, Jette L.; Ransohoff, R M.
In: The Journal of Clinical Investigation, Vol. 103, No. 6, 03.1999, p. 807-15.Research output: Contribution to journal › Journal article › Research
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TY - JOUR
T1 - Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients
AU - Sørensen, Torben Lykke
AU - Tani, M
AU - Jensen, J
AU - Pierce, V
AU - Lucchinetti, C
AU - Folcik, V A
AU - Qin, Shuyuan
AU - Rottman, J
AU - Sellebjerg, F
AU - Strieter, R M
AU - Frederiksen, Jette L.
AU - Ransohoff, R M
PY - 1999/3
Y1 - 1999/3
N2 - Chemokines direct tissue invasion by specific leukocyte populations. Thus, chemokines may play a role in multiple sclerosis (MS), an idiopathic disorder in which the central nervous system (CNS) inflammatory reaction is largely restricted to mononuclear phagocytes and T cells. We asked whether specific chemokines were expressed in the CNS during acute demyelinating events by analyzing cerebrospinal fluid (CSF), whose composition reflects the CNS extracellular space. During MS attacks, we found elevated CSF levels of three chemokines that act toward T cells and mononuclear phagocytes: interferon-gamma-inducible protein of 10 kDa (IP-10); monokine induced by interferon-gamma (Mig); and regulated on activation, normal T-cell expressed and secreted (RANTES). We then investigated whether specific chemokine receptors were expressed by infiltrating cells in demyelinating MS brain lesions and in CSF. CXCR3, an IP-10/Mig receptor, was expressed on lymphocytic cells in virtually every perivascular inflammatory infiltrate in active MS lesions. CCR5, a RANTES receptor, was detected on lymphocytic cells, macrophages, and microglia in actively demyelinating MS brain lesions. Compared with circulating T cells, CSF T cells were significantly enriched for cells expressing CXCR3 or CCR5. Our results imply pathogenic roles for specific chemokine-chemokine receptor interactions in MS and suggest new molecular targets for therapeutic intervention.
AB - Chemokines direct tissue invasion by specific leukocyte populations. Thus, chemokines may play a role in multiple sclerosis (MS), an idiopathic disorder in which the central nervous system (CNS) inflammatory reaction is largely restricted to mononuclear phagocytes and T cells. We asked whether specific chemokines were expressed in the CNS during acute demyelinating events by analyzing cerebrospinal fluid (CSF), whose composition reflects the CNS extracellular space. During MS attacks, we found elevated CSF levels of three chemokines that act toward T cells and mononuclear phagocytes: interferon-gamma-inducible protein of 10 kDa (IP-10); monokine induced by interferon-gamma (Mig); and regulated on activation, normal T-cell expressed and secreted (RANTES). We then investigated whether specific chemokine receptors were expressed by infiltrating cells in demyelinating MS brain lesions and in CSF. CXCR3, an IP-10/Mig receptor, was expressed on lymphocytic cells in virtually every perivascular inflammatory infiltrate in active MS lesions. CCR5, a RANTES receptor, was detected on lymphocytic cells, macrophages, and microglia in actively demyelinating MS brain lesions. Compared with circulating T cells, CSF T cells were significantly enriched for cells expressing CXCR3 or CCR5. Our results imply pathogenic roles for specific chemokine-chemokine receptor interactions in MS and suggest new molecular targets for therapeutic intervention.
KW - Acute Disease
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Central Nervous System
KW - Chemokine CCL5
KW - Chemokine CXCL10
KW - Chemokine CXCL9
KW - Chemokines
KW - Chemokines, CXC
KW - Female
KW - Humans
KW - Intercellular Signaling Peptides and Proteins
KW - Male
KW - Middle Aged
KW - Multiple Sclerosis
KW - Receptors, CCR5
KW - Receptors, Chemokine
KW - Receptors, Cytokine
KW - T-Lymphocytes
U2 - 10.1172/JCI5150
DO - 10.1172/JCI5150
M3 - Journal article
C2 - 10079101
VL - 103
SP - 807
EP - 815
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 6
ER -
ID: 111410843