RESUMO
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.
Assuntos
Barreira Hematoencefálica/imunologia , Metaloproteinase 9 da Matriz/líquido cefalorraquidiano , Doenças do Sistema Nervoso/imunologia , Doenças do Sistema Nervoso/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Esclerose Lateral Amiotrófica/imunologia , Esclerose Lateral Amiotrófica/metabolismo , Líquido Cefalorraquidiano/citologia , Líquido Cefalorraquidiano/enzimologia , Quimiotaxia de Leucócito/imunologia , Criança , Feminino , Granulócitos/citologia , Granulócitos/imunologia , Síndrome de Guillain-Barré/imunologia , Síndrome de Guillain-Barré/metabolismo , Humanos , Neuroborreliose de Lyme/imunologia , Neuroborreliose de Lyme/metabolismo , Masculino , Metaloproteinase 1 da Matriz/sangue , Metaloproteinase 1 da Matriz/líquido cefalorraquidiano , Metaloproteinase 9 da Matriz/sangue , Meningites Bacterianas/imunologia , Meningites Bacterianas/metabolismo , Meningite Viral/imunologia , Meningite Viral/metabolismo , Pessoa de Meia-Idade , Esclerose Múltipla/imunologia , Esclerose Múltipla/metabolismoRESUMO
Matrix metalloproteinase-9 (MMP-9) and its specific inhibitor, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), were analysed by enzyme-linked immunosorbent assay (ELISA) and by zymography in serum and cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS). In contrast to patients with inflammatory diseases, MMP-9 levels were not elevated in CSF of ALS patients. In serum, however, compared to healthy donors, MMP-9 was significantly (p = 0.0003) increased up to levels as high as those of viral meningoencephalitis (VM) or bacterial meningitis (BM) patients. MMP-9 levels remained elevated during long-term observation of ALS patients. In the absence of an inflammatory response, the results indicate that the increase of MMP-9 in serum of ALS patients might be caused by upregulation of MMP-9 in denervated muscles or in degenerating peripheral nerves following motor neurone loss.