Your browser doesn't support javascript.
loading
MMP (Matrix Metalloprotease)-9-Producing Monocytes Enable T Cells to Invade the Vessel Wall and Cause Vasculitis.
Watanabe, Ryu; Maeda, Toshihisa; Zhang, Hui; Berry, Gerald J; Zeisbrich, Markus; Brockett, Robert; Greenstein, Andrew E; Tian, Lu; Goronzy, Jörg J; Weyand, Cornelia M.
Afiliación
  • Watanabe R; From the Division of Immunology and Rheumatology, Department of Medicine (R.W., T.M., H.Z., M.Z., J.J.G., C.M.W.).
  • Maeda T; From the Division of Immunology and Rheumatology, Department of Medicine (R.W., T.M., H.Z., M.Z., J.J.G., C.M.W.).
  • Zhang H; From the Division of Immunology and Rheumatology, Department of Medicine (R.W., T.M., H.Z., M.Z., J.J.G., C.M.W.).
  • Berry GJ; Department of Pathology (G.J.B.).
  • Zeisbrich M; From the Division of Immunology and Rheumatology, Department of Medicine (R.W., T.M., H.Z., M.Z., J.J.G., C.M.W.).
  • Brockett R; Gilead Sciences, Inc, Foster City, CA (R.B., A.E.G.).
  • Greenstein AE; Gilead Sciences, Inc, Foster City, CA (R.B., A.E.G.).
  • Tian L; Department of Biomedical Data Science, Stanford University School of Medicine, CA (L.T.).
  • Goronzy JJ; From the Division of Immunology and Rheumatology, Department of Medicine (R.W., T.M., H.Z., M.Z., J.J.G., C.M.W.).
  • Weyand CM; From the Division of Immunology and Rheumatology, Department of Medicine (R.W., T.M., H.Z., M.Z., J.J.G., C.M.W.).
Circ Res ; 123(6): 700-715, 2018 08 31.
Article en En | MEDLINE | ID: mdl-29970365
RATIONALE: Giant cell arteritis (GCA)-a primary vasculitis of medium and large arteries-is associated with vessel wall damage, elastic membrane fragmentation, and vascular remodeling. Proteinases are believed to contribute to pathogenesis by degrading extracellular matrix and causing tissue injury. OBJECTIVE: The MMP (matrix metalloproteinase)-9-a type IV collagenase-is produced in the vasculitic lesions of GCA. It is unknown which pathogenic processes are MMP-9 dependent. METHODS AND RESULTS: The tissue transcriptome of GCA-affected temporal arteries contained high amounts of MMP-9 transcripts, and immunostaining for pro-MMP-9 localized the enzyme to wall-infiltrating macrophages. MMP-2 and MMP-9 transcripts were also abundant in monocytes and monocyte-derived macrophages from patients with GCA. Patient-derived monocytes outperformed healthy monocytes in passing through engineered basement membranes. GCA CD (cluster of differentiation) 4+ T cells required MMP-9-producing monocytes to penetrate through matrix built from type IV collagen. In vivo functions of MMP-9 were tested in a human artery-SCID (severe combined immunodeficiency) chimera model by blocking enzyme activity with a highly specific monoclonal antibody or by injecting rMMP-9 (recombinant MMP-9). Inhibiting MMP-9 activity profoundly suppressed vascular injury, decreased the density of inflammatory infiltrates ( P<0.001), reduced intramural neoangiogenesis ( P<0.001), and prevented intimal layer hyperplasia ( P<0.001). rMMP-9 amplified all domains of vasculitic activity, promoted assembly of T-cell infiltrates ( P<0.05), intensified formation of new microvessels ( P<0.001), and worsened intimal thickening ( P<0.001). Systemic delivery of N-acetyl-proline-glycine-proline-a matrikine produced by MMP-9-mediated gelatinolysis-had limited vasculitogenic effects. CONCLUSIONS: In large vessel vasculitis, MMP-9 controls the access of monocytes and T cells to the vascular wall. T cells depend on MMP-9-producing monocytes to pass through collagen IV-containing basement membrane. Invasion of vasculitogenic T cells and monocytes, formation of neoangiogenic networks, and neointimal growth all require the enzymatic activity of MMP-9, identifying this protease as a potential therapeutic target to restore the immunoprivilege of the arterial wall in large vessel vasculitis.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Arteria Axilar / Arterias Temporales / Arteritis de Células Gigantes / Monocitos / Linfocitos T CD4-Positivos / Movimiento Celular / Metaloproteinasa 9 de la Matriz / Remodelación Vascular Tipo de estudio: Observational_studies / Risk_factors_studies Límite: Aged80 Idioma: En Revista: Circ Res Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Arteria Axilar / Arterias Temporales / Arteritis de Células Gigantes / Monocitos / Linfocitos T CD4-Positivos / Movimiento Celular / Metaloproteinasa 9 de la Matriz / Remodelación Vascular Tipo de estudio: Observational_studies / Risk_factors_studies Límite: Aged80 Idioma: En Revista: Circ Res Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos