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A mechanism for neutrophil-mediated lysis of human neuroblastoma-cells

Academic Article
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Overview

authors

  • Barker, E.
  • Reisfeld, Ralph

publication date

  • January 1993

journal

  • Cancer Research  Journal

abstract

  • Neutrophils mediate the lysis of human neuroblastoma cells coated with human/mouse chimeric anti-GD2 ganglioside antibody ch14.18. This study examined the mechanism(s) by which this occurs. Neutrophil degranulation was found to be a required step for lysis, since release of granular enzymes from neutrophils correlated with the lysis of antibody-coated neuroblastoma cells. In addition, agents which block degranulation specifically inhibited this process. Antibody-dependent lysis of neuroblastoma cells was enhanced by exposing neutrophils to granulocyte-macrophage colony stimulatory factor. An increased release of lytic granular molecules was found to be responsible for this lymphokine-mediated phenomenon. Among the molecules released from neutrophil granules that were shown to be involved in neuroblastoma cell lysis were defensins, M(r) 3000-4000 neutrophil granular proteins which are known to bind and permeabilize tumor cells. In addition, cathepsin-G, a neutrophil granular protease, was demonstrated for the first time to mediate the lysis of human neuroblastoma cells. The enzymatic activity of cathepsin-G was found to be required for the lysis of these tumor cells, since phenylmethylsulfonyl fluoride blocks the lytic ability of this protein.

subject areas

  • Antibodies, Neoplasm
  • Antibody-Dependent Cell Cytotoxicity
  • Blood Proteins
  • Cathepsin G
  • Cathepsins
  • Cell Degranulation
  • Cytotoxicity, Immunologic
  • Defensins
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Humans
  • In Vitro Techniques
  • Neuroblastoma
  • Neutrophils
  • Pancreatic Elastase
  • Serine Endopeptidases
  • Tumor Cells, Cultured
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Identity

International Standard Serial Number (ISSN)

  • 0008-5472

PubMed ID

  • 8417829
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Additional Document Info

start page

  • 362

end page

  • 367

volume

  • 53

issue

  • 2

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