Vascular cell adhesion molecule-1-mediated matrix metalloproteinase-2 induction in peripheral blood T cells is up-regulated in patients with HTLV-I-associated myelopathy

We investigated whether matrix metalloproteinase-2 (MMP-2) is induced in pe ripheral blood T cells after their contact with tumor necrosis factor-alpha . (TNF-alpha)-stimulated glioblastoma cell line (T98G), expressing vascular cell adhesion molecule-1 (VCAM-I), in patients with HTLV-I-associated myel opathy (HAM) compared to control patients with other neurological disorders (OND), Gelatin zymography revealed that the incremental ratio of gelatinol ytic activity of MMP-2 in culture supernatants derived from T cells cocultu red with TNF-alpha-stimulated T98G to that of supernatants derived from cul tures of T cells alone was significantly higher in HAM patients than in con trol patients with OND. Immunoblot analysis of immunoprecipitates of cultur e supernatant showed that increased gelatinolytic activity of MMP-2 was due to increased production of MMP-2 protein in T cells. Increased gelatinolyt ic activity of MMP-2 in T cells of HAM patients was blocked by pretreatment of TNF-alpha-stimulated T98G with anti-VCAM-1 antibody before coculture wi th T cells, indicating that MMP-2 induction was VCAM-1-mediated. Although n o significant differences were noted in the percentage of VLA-4-positive ce lls in cultured T cells between HAM patients and control patients with OND, our results indicate that VCAM-1-mediated MMP-2, induction is up-regulated in T cells of HAM patients. (C) 1999 Elsevier Science B.V. All rights rese rved.