Chemokines and matrix metalloproteinase-9 in leukocyte recruitment to the central nervous system

TY - JOUR

T1 - Chemokines and matrix metalloproteinase-9 in leukocyte recruitment to the central nervous system

AU - Sellebjerg, F.

AU - Sørensen, T. L.

PY - 2003/8/15

Y1 - 2003/8/15

N2 - Chemokines and matrix metalloproteinases (MMPs) play key roles in leukocyte migration across the blood-brain barrier (BBB) in infectious and inflammatory diseases, including multiple sclerosis (MS). In MS some chemokine receptors are expressed by an increased percentage of T cells in blood, the CSF concentration of chemokine ligands for these receptors is increased, and there is accumulation of T cells expressing relevant chemokine receptors in CSF and in the CNS parenchyma. Chemokine receptor expression patterns appear to reflect disease activity and disease stage in MS. MMPs are constitutively expressed or induced by proinflammatory cytokines and chemokines in leukocytes and CNS-resident cells. Several MMPs are expressed in MS plaques, and the CSF concentration of MMP-9 is increased in MS. The CSF concentration of MMP-9 may reflect disease activity in MS, and the CSF concentration of MMP-9 is higher in patients carrying the MS-associated HLA type DRB1*1501. We review how chemokines and MMP-9 may be involved in the pathogenesis of MS by controlling leukocyte migration between different functional compartments. Measuring expression of these molecules may find use as surrogate markers of disease activity in MS, and interfering with their function holds promise as a novel therapeutic strategy in MS.

AB - Chemokines and matrix metalloproteinases (MMPs) play key roles in leukocyte migration across the blood-brain barrier (BBB) in infectious and inflammatory diseases, including multiple sclerosis (MS). In MS some chemokine receptors are expressed by an increased percentage of T cells in blood, the CSF concentration of chemokine ligands for these receptors is increased, and there is accumulation of T cells expressing relevant chemokine receptors in CSF and in the CNS parenchyma. Chemokine receptor expression patterns appear to reflect disease activity and disease stage in MS. MMPs are constitutively expressed or induced by proinflammatory cytokines and chemokines in leukocytes and CNS-resident cells. Several MMPs are expressed in MS plaques, and the CSF concentration of MMP-9 is increased in MS. The CSF concentration of MMP-9 may reflect disease activity in MS, and the CSF concentration of MMP-9 is higher in patients carrying the MS-associated HLA type DRB1*1501. We review how chemokines and MMP-9 may be involved in the pathogenesis of MS by controlling leukocyte migration between different functional compartments. Measuring expression of these molecules may find use as surrogate markers of disease activity in MS, and interfering with their function holds promise as a novel therapeutic strategy in MS.

KW - Cerebrospinal fluid

KW - Inflammatory demyelination

KW - Macrophages

KW - Multiple sclerosis

KW - T cells

UR - http://www.scopus.com/inward/record.url?scp=0042591142&partnerID=8YFLogxK

U2 - 10.1016/S0361-9230(03)00097-2

DO - 10.1016/S0361-9230(03)00097-2

M3 - Journal article

C2 - 12909304

AN - SCOPUS:0042591142

SN - 0361-9230

VL - 61

SP - 347

EP - 355

JO - Brain Research Bulletin

JF - Brain Research Bulletin

IS - 3

ER -