The release of cytotoxic granule contents by cytotoxic T lymphocytes triggers apoptotic target cell death. Cytotoxic granules contain a pore-forming protein, perforin, and a group of serine proteases called granzymes. We expressed human granzyme A in bacteria as a proenzyme capable of in vitro activation by enterokinase. The recombinant activated enzyme has catalytic activity against substrates...

When death starts with a caspase hen a cytotoxic lymphocyte delivers granzyme B to a target cell, current models emphasize that the enzyme induces apoptosis through a mitochondria-centered pathway, cleaving the proapoptotic Bcl-2 family member Bid to cause mitochondrial permeabilization. On page 875, Metkar et al. overturn this view, showing that in the dominant pathway granzyme B begins by pro...

Cytotoxic lymphocytes possess a number of serine proteases (granzymes) usually localized in cytoplasmic granules. To date, the DNA sequences of four human granzymes have been reported. A fifth human granzyme (granzyme 3) has been biochemically purified and its N-terminal amino acid sequence has been reported. This enzyme was described as possessing tryptase activity, cleaving synthetic substrat...

Granzymes are a family of granule-associated serine esterases that mediate apoptosis by cytotoxic T lymphocytes and natural killer cells. We have previously shown that cdc2, the mitosis-regulating cyclin-dependent kinase, is required for granzyme B-induced apoptosis in target cells. In addition, granzyme B induces premature activation and tyrosine dephosphorylation of cdc2 during apoptosis. Thr...

When death starts with a caspase hen a cytotoxic lymphocyte delivers granzyme B to a target cell, current models emphasize that the enzyme induces apoptosis through a mitochondria-centered pathway, cleaving the proapoptotic Bcl-2 family member Bid to cause mitochondrial permeabilization. On page 875, Metkar et al. overturn this view, showing that in the dominant pathway granzyme B begins by pro...

BACKGROUND AND AIMS Colorectal cancer (CRC) harbours different types of DNA alterations, including microsatellite instability (MSI). Cancers with high levels of MSI (MSI-H) are considered to have a good prognosis, probably related to lymphocyte infiltration within tumours. The aim of the present study was to characterise the intratumoural expression of markers associated with the antitumour imm...

INTRODUCTION Leishmania braziliensis infection induces a large spectrum of lesions that clinically manifest as nodules or papules that progress to ulcers. Although it is already known that T helper cells predominate in the lesions, cytotoxic T cells have also been reported to be present, and their role in leishmaniasis immunopathogenesis is not well known. This study investigated the amounts of...

Survivin is an antiapoptotic protein highly expressed in malignant cells that confers resistance to cytotoxic therapy. Granzyme B is a potent cytotoxic protein that is released from mammalian natural killer cells and CTLs following noxious stimuli, including foreign invaders. Here, we took advantage of the properties of these two functionally divergent molecules to create a molecular agent that...

Histamine, leukotriene C4, IL-4, and IL-13 are major mediators of allergy and asthma. They are all formed by basophils and are released in particularly large quantities after stimulation with IL-3. Here we show that supernatants of activated mast cells or IL-3 qualitatively change the makeup of granules of human basophils by inducing de novo synthesis of granzyme B (GzmB), without induction of ...

BACKGROUND Whereas the presence of a lymphoid infiltrate has been associated with a favourable prognosis in colorectal carcinoma, the proliferative and cytotoxic responses of freshly isolated tumour infiltrating lymphocytes are frequently impaired. In mice, tumour induced immune suppression has been associated with a decreased expression of the zeta-chain of the T cell receptor (TCR)-CD3 comple...