Matrix metalloproteinase-9 (MMP-9) in human cerebrospinal fluid (CSF): elevated levels are primarily related to CSF cell count.
Matrix metalloproteinase-9 (MMP-9) was investigated by enzyme-linked immunosorbent assay (ELISA) and zymography in 111 paired CSF and serum samples from patients with various neurological disorders. In 20 patients with blood-brain barrier (BBB) impairment but normal CSF cell count, elevated levels of MMP-9 were not observed by ELISA measurement. Another 11 patients characterized in the same way, exhibited only slightly increased MMP-9 levels. In contrast, in 12 patients with intact BBB but elevated CSF cell count, MMP-9 was increased too. It was shown by the more sensitive zymography that MMP-9 increased if CSF cell count exceeded five cells per microl. Spearman rank statistics revealed that MMP-9 concentration in CSF correlated with CSF cell count (r=0.755; P<0.0001), but not with CSF/serum albumin ratio (Q(Alb)) (r=0.212; P=0.057), a measure for BBB impairment. Moreover, the CSF/serum MMP-9 ratio (Q(MMP-9)) did not correlate with Q(Alb)(r=0.192; P=0.100). By use of a Boyden chamber, in which granulocytes migrated through a reconstituted basement membrane, it was demonstrated that the MMP-9 concentration in the lower chamber correlated very significantly with the number of accumulated cells (r(2)=0.7692; P<0.0001). The meaning of the increase of MMP-9 in CSF is critically discussed.
Yushchenko
M
M
Department of Neurology, Georg-August-University, Robert-Koch-Str. 40, D-37075, Göttingen, Germany.
Weber
F
F
Mäder
M
M
Schöll
U
U
Maliszewska
M
M
Tumani
H
H
Felgenhauer
K
K
Beuche
W
W
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000276:immunology / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000276:immunology*; D002555:Cerebrospinal Fluid / Q000166:cytology / Q000201:enzymology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D002648:Child; D005260:Female; D006098:Granulocytes / Q000166:cytology / Q000276:immunology; D020275:Guillain-Barre Syndrome / Q000276:immunology / Q000378:metabolism; D006801:Humans; D020852:Lyme Neuroborreliosis / Q000276:immunology / Q000378:metabolism; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000097:blood / Q000134:cerebrospinal fluid; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000134:cerebrospinal fluid*; D016920:Meningitis, Bacterial / Q000276:immunology / Q000378:metabolism; D008587:Meningitis, Viral / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism; D009422:Nervous System Diseases / Q000276:immunology* / Q000378:metabolism*
D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1