Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in HTLV-I-associated myelopathy

• Published in: Journal of neuropathology and experimental neurology Vol. 57; no. 9; pp. 839 - 849
• Main Authors: UMEHARA, F, OKADA, Y, FUJIMOTO, N, ABE, M, IZUMO, S, OSAME, M
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.09.1998; Oxford University Press
• Subjects: Aged; AIDS/HIV; Biological and medical sciences; Collagenases - biosynthesis; Collagenases - cerebrospinal fluid; Female; Gelatinases - biosynthesis; Gelatinases - cerebrospinal fluid; HTLV-I Infections - cerebrospinal fluid; HTLV-I Infections - metabolism; HTLV-I Infections - pathology; Human T-lymphotropic virus 1; Human viral diseases; Humans; Infectious diseases; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; matrix metalloproteinases; Medical sciences; Metalloendopeptidases - analysis; Metalloendopeptidases - biosynthesis; Metalloendopeptidases - cerebrospinal fluid; Middle Aged; myelopathy; Paraparesis, Tropical Spastic - cerebrospinal fluid; Paraparesis, Tropical Spastic - metabolism; Paraparesis, Tropical Spastic - pathology; Spinal Cord - metabolism; Spinal Cord - pathology; Tissue Inhibitor of Metalloproteinases - analysis; Tissue Inhibitor of Metalloproteinases - biosynthesis; Tissue Inhibitor of Metalloproteinases - cerebrospinal fluid; Viral diseases; Viral diseases of the nervous system; Human; Nervous system diseases; Motor system disorder; Pathogenesis; Retroviridae; Spasticity; Enzyme inhibitor; Muscle tonus alteration; Paraparesia; Gene expression; Infection; Virus; Myelopathy; Striated muscle disease; Viral disease; Paresis; Central nervous system disease; Neurological disorder; HTLV-I virus; Spinal cord disease
• ISSN: 0022-3069; 1554-6578
• DOI: 10.1097/00005072-199809000-00005

Matrix metalloproteinases (MMPs) have been reported to be involved in inflammatory disorders of the central nervous system (CNS). However, little is known about the role of MMPs in the pathogenesis of HTLV-I-associated myelopathy (HAM)/Tropical spastic paraparesis (TSP). To address this issue, we examined the tissue expression and localization of MMPs and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs) in the spinal cord lesions of HAM/TSP using immunohistochemistry. In addition, the blood and cerebrospinal fluid (CSF) levels of MMPs and TIMPs of the patients with HAM/TSP were determined using sandwich enzyme immunoassays (SIA) and gelatin zymography. Immunohistochemical studies revealed that collagen IV and decorin immunoreactivity on the basement membrane of CNS parenchymal vessels was partially disrupted where inflammatory mononuclear cells infiltrated in active-chronic lesions of HAM/TSP. In these lesions, MMP-2 (gelatinase A) was immunostained mainly on the surface of foamy macrophages and lymphocytes, whereas MMP-9 (gelatinase B) expression was positive in the intravascular and perivascular mononuclear cells but not on foamy macrophages. In contrast, inactive chronic lesions of the spinal cords of the HAM/TSP contained fewer MMP-2-positive or MMP-9-positive mononuclear cells than active-chronic lesions. Many parenchymal vessels had thickened vascular walls which showed increased immunoreactivity to decorin. SIA revealed that production levels of MMP-2 and MMP-9 in both blood and CSF were higher in the patients with HAM/TSP than those in non-inflammatory other neurological disease controls (ONDs). Using zymography, proMMP-9 was detected more frequently in the CSF of patients with HAM/TSP than those in ONDs. Taken together, our data indicate that MMP-2 and MMP-9 may play an important role in the blood-brain barrier breakdown and tissue remodeling in the CNS of HAM/TSP.