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 peripheral 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-1), in patients with HTLV-I-associated myelopathy (HAM) compared to control patients with other neurological disorders (OND). Gelatin zymography revealed that the incremental ratio of gelatinolytic activity of MMP-2 in culture supernatants derived from T cells cocultured with TNF-alpha-stimulated T98G to that of supernatants derived from cultures of T cells alone was significantly higher in HAM patients than in control patients with OND. Immunoblot analysis of immunoprecipitates of culture supernatant showed that increased gelatinolytic activity of MMP-2 was due to increased production of MMP-2 protein in T cells. Increased gelatinolytic 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 with T cells, indicating that MMP-2 induction was VCAM-1-mediated. Although no significant differences were noted in the percentage of VLA-4-positive cells 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.
Kambara
C
C
First Department of Internal Medicine, Nagasaki University School of Medicine, Sakamoto, Japan.
Nakamura
T
T
Furuya
T
T
Migita
K
K
Ida
H
H
Kawakami
A
A
Shirabe
S
S
Nakane
S
S
Kinoshita
I
I
Eguchi
K
K
D000328:Adult; D000368:Aged; D018926:Anti-Allergic Agents / Q000032:analysis / Q000378:metabolism; D000906:Antibodies / Q000494:pharmacology; D017951:Antigen Presentation / Q000276:immunology; D004789:Enzyme Activation / Q000276:immunology; D005260:Female; D005780:Gelatin; D018093:Gelatinases / Q000276:immunology / Q000378:metabolism*; D005909:Glioblastoma; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000032:analysis / Q000096:biosynthesis; D008297:Male; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000276:immunology* / Q000378:metabolism*; D016201:Receptors, Lymphocyte Homing / Q000032:analysis / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000737:chemistry / Q000166:cytology / Q000201:enzymology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism*
D018926:Anti-Allergic Agents; D000906:Antibodies; D039041:Integrin alpha4beta1; D016023:Integrins; D016201:Receptors, Lymphocyte Homing; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D005780:Gelatin; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2