Extracellular granzymes A and B in humans: detection of native species during CTL responses in vitro and in vivo: detection of native species during CTL responses in vitro and in vivo

E. H. Spaeny-Dekking, W. L. Hanna, A. M. Wolbink, P. C. Wever, J. A. Kummer, A. J. Kummer, A. J. Swaak, J. M. Middeldorp, H. G. Huisman, C. J. Froelich, C. E. Hack

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172 Citations (Scopus)


Activated CTLs and NK cells induce apoptosis via multiple mechanisms, including that termed granule exocytosis. The latter pathway consists of vectorial secretion of perforin and a family of granule-associated serine proteases (granzymes) to the target cell. To establish whether granzymes are released extracellularly during cytolytic reactions in vivo, ELISAs that measure the native enzymes were developed and were found to specifically detect granzyme A (GrA) and granzyme B (GrB) at picogram concentrations. Low levels of GrA and GrB were present in plasma of healthy individuals (GrA, 33.5 pg/ml (median); GrB, 11.5 pg/ml (median)), whereas significantly higher levels were present in patients with ongoing CTL response, i.e., patients suffering from infections by EBV or HIV type 1. Markedly elevated levels were also noted in synovial fluid of patients with active rheumatoid arthritis. The measurement of soluble granzymes should be useful to assess clinical disorders associated with activated CTL and NK cells. Furthermore, these results suggest that granzymes mediate biologic effects beyond their described role in apoptotic cell death
Original languageEnglish
Pages (from-to)3610-3616
Number of pages7
JournalJournal of immunology (Baltimore, Md.
Issue number7
Publication statusPublished - 1 Apr 1998


  • Animals
  • Antibodies, Monoclonal
  • Antibody Specificity
  • Arthritis, Rheumatoid
  • Cell Degranulation
  • Cells, Cultured
  • Enzyme-Linked Immunosorbent Assay
  • Extracellular Space
  • Granzymes
  • HIV Infections
  • HIV-1
  • Herpesvirus 4, Human
  • Humans
  • Infectious Mononucleosis
  • Injections, Subcutaneous
  • Journal Article
  • Longitudinal Studies
  • Mice
  • Mice, Inbred BALB C
  • Research Support, Non-U.S. Gov't
  • Serine Endopeptidases
  • Solubility
  • Synovial Fluid
  • T-Lymphocytes, Cytotoxic
  • Tumor Cells, Cultured

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