'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 ... More
Granzyme B directly and efficiently cleaves several downstream caspase substrates: implications for CTL-induced apoptosis.
AuthorsAndrade F, Roy S, Nicholson D, Thornberry N, Rosen A, Casciola-Rosen L
JournalImmunity
PubMed ID9586635
'Caspase-mediated proteolysis of downstream substrates is a critical element of the execution pathway common to all forms of apoptosis studied to date. While this caspase-dependent pathway is activated during cytotoxic lymphocyte granule-induced cell death, recent studies have also provided evidence for caspase-independent pathways. However, the mechanisms mediating these additional pathways ... More
Production and characterization of monoclonal antibodies raised against recombinant human granzymes A and B and showing cross reactions with the natural proteins.
AuthorsKummer JA, Kamp AM, van Katwijk M, Brakenhoff JP, Radosevic K, van Leeuwen AM, Borst J, Verweij CL, Hack CE
JournalJ Immunol Methods
PubMed ID7687640
The human serine proteases granzymes A and B are expressed in cytoplasmic granules of activated cytotoxic T lymphocytes and natural killer cells. Recombinant granzyme A and granzyme B proteins were produced in bacteria, purified and then used to raise specific mouse monoclonal antibodies. Seven monoclonal antibodies (mAb) were raised against ... More
Role of perforin, granzymes and the proliferative state of the target cells in apoptosis and necrosis mediated by bispecific-antibody-activated cytotoxic T cells.
AuthorsRenner C, Held G, Ohnesorge S, Bauer S, Gerlach K, Pfitzenmeier JP, Pfreundschuh M
JournalCancer Immunol Immunother
PubMed ID9177467
Bispecific monoclonal antibodies (bi-mAb), directed against a tumor-associated antigen and the CD3 or CD28 antigen on T lymphocytes, induce activation of resting T lymphocytes and target-specific tumor cell lysis. We now show that both necrosis and apoptosis contribute to T-cell-mediated tumor cell destruction. Even though T cells up-regulate FAS/APO-1 expression ... More
Localization and identification of granzymes A and B-expressing cells in normal human lymphoid tissue and peripheral blood.
AuthorsKummer JA, Kamp AM, Tadema TM, Vos W, Meijer CJ, Hack CE
JournalClin Exp Immunol
PubMed ID7697916
Cytoplasmic granules from activated natural killer (NK) and cytotoxic T lymphocytes (CTL) contain a pore-forming protein, perforin, and several homologous serine proteinases called granzymes. Expression of these proteins correlates with the cytolytic potential of cytotoxic lymphocytes. Using a panel of MoAbs specific for human granzyme A and B, respectively, expression ... More
Granzyme B (GraB) autonomously crosses the cell membrane and perforin initiates apoptosis and GraB nuclear localization.
Granzyme B (GraB) induces apoptosis in the presence of perforin. Perforin polymerizes in the cell membrane to form a nonspecific ion pore, but it is not known where GraB acts to initiate the events that ultimately lead to apoptosis. It has been hypothesized that GraB enters the target cell through ... More
Granzyme B and perforin lytic proteins are expressed in CD34+ peripheral blood progenitor cells mobilized by chemotherapy and granulocyte colony-stimulating factor.
AuthorsBerthou C, Marolleau JP, Lafaurie C, Soulié A, Dal Cortivo L, Bourge JF, Benbunan M, Sasportes M
JournalBlood
PubMed ID7579456
Granzyme B and perforin are cytoplasmic granule-associated proteins used by cytotoxic T lymphocytes and natural killer (NK) cells to kill their targets. However, granzyme B gene expression has also been detected in a non-cytotoxic hematopoietic murine multipotent stem cell line, FDCP-Mix. The objective of the present study was to investigate ... More
Anti-CD3-activated killer T cells: interferon-gamma and interleukin-10 cross-regulate granzyme B expression and the induction of major histocompatibility complex-unrestricted cytotoxicity.
AuthorsFitzpatrick L, Makrigiannis AP, Kaiser M, Hoskin DW
JournalJ Interferon Cytokine Res
PubMed ID8836920
We have investigated the effect of interferon-gamma (IFN-gamma) and interleukin (IL)-10 on granzyme B expression and the induction of major histocompatibility complex (MHC)-unrestricted cytotoxic activity in mouse T cell cultures following activation with anti-CD3 monoclonal antibody (mAb). First, metabolic inhibitors of granule-dependent and granule-independent cytolytic pathways were used to show ... More
Granzyme release and caspase activation in activated human T-lymphocytes.
Recently it has been reported that caspase-3 activation occurs in stimulated T-lymphocytes without associated apoptosis (Miossec, C., Dutilleul, V., Fassy, F., and Diu-Hercend, A. (1997) J. Biol. Chem. 272, 13459-13462). To explore this phenomenon, human peripheral blood lymphocytes (PBLs) were stimulated with mitogenic lectins or anti-CD3 antibody, and the proteolytic ... More