Increased activity of matrix metalloproteinases and their tissue inhibitors in cerebrospinal fluid of patients with HTLV-1 associated tropical spastic paraparesis

Background: Proteolytic modifications of neuronal surfaces and the surround ing extracellular matrix are ver important in neuronal development and rege neration. Increased activity of matrix metalloproteinases (MMPs) and their tissue inhibitors, due to secretion by macrophages and lymphocytes, occur i n inflammatory processes that disrupt the blood brain barrier. However, neu rons and microglia can also secrete these enzymes. Aim: To identify the typ e of MMP present in the cerebrospinal fluid (CSF) and changes in the expres sion of tissue inhibitors of metalloproteinases (TIMPs) in patients wit HTL V-1 associated tropical spastic paraparesis. Patients adn methods: CSF samp les from 12 patients with HTLV-1 associated tropical spastic paraparesis an d 12 healthy controls were obtained by an atraumatic lumbar puncture. The p resence of MMPs was measured by zymography and the relative amounts of TIMP s were measured by immunowestern blot. Results: In the CSF of both controls and patients, a similar gelatinolytic band corresponding to proMMP-2 (late nt form) was observed. In 83.3% of patients with HTLV 1 associated tropical spastic paraparesis, the MMP-9 wa also present. TIMP-1, TIMP-2 and TIMP-3 were elevated 2.24 +/- 0.72, 3.85 +/- 1.38 and 5.89 +/- 3.4 fold, respectiv ely, in the CSF of patients as compared to controls. Conclusions: Patients with HTLV-1 associated tropical spastic paraparesis have elevated activity of MMP-9 and levels of TIMPs in the CSF, when compared to healthy controls.