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Human T-lymphocyte serine proteases (granzymes) 1, 2, and 3 mediated DNA fragmentation in susceptible target cells.
Hameed, A; Schafer, R W; Sundaresan, V D; Vaccarello, L.
Afiliación
  • Hameed A; Department of Pathology, Ohio State University, Columbus 43210, USA.
Hum Immunol ; 49(1): 13-21, 1996 Aug.
Article en En | MEDLINE | ID: mdl-8839771
We reported the characterization of three serine proteases (granzymes 1, 2, and 3) from human cytotoxic T lymphocytes. In this study, human granzymes 1, 2, and 3 were purified from the cytoplasmic granules of lymphokine activated killer (LAK) cells by gel filtration and cation exchange chromatography. Human perforin was purified by phenyl superose and heparin-agarose chromatography. Each purified granzyme was used with purified perforin to study DNA fragmentation in target cells of both human and murine origin. As measured by agarose gel electrophoresis and [125I]dUrd assay, the granzymes induced oligonucleosomal DNA fragmentation and [125I]dUrd release respectively from various target cells. Murine target cells were generally more susceptible to nuclear DNA release than were human targets. Both enzyme activity and nuclear DNA breakdown were significantly inhibited by 3,4-dichloroisocoumarin (DCI) or by heat inactivation of each granzyme. Perforin alone or granzyme alone failed to fragment nuclear DNA in various target cells. We conclude that human granzymes are an important family of effector molecules that with perforin induce DNA fragmentation in susceptible target cells.
Asunto(s)
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Serina Endopeptidasas / Linfocitos T Citotóxicos / Células Asesinas Activadas por Linfocinas / Fragmentación del ADN Límite: Humans Idioma: En Revista: Hum Immunol Año: 1996 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Serina Endopeptidasas / Linfocitos T Citotóxicos / Células Asesinas Activadas por Linfocinas / Fragmentación del ADN Límite: Humans Idioma: En Revista: Hum Immunol Año: 1996 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos