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Products for Granzyme B Research
 | | |  View Granzyme B products | | | CTL and NK cells are key components of the host defense system against virus-infected and malignant cells. The major mechanism responsible for cell lysis in these cells is the granule exocytose pathway. Upon binding of the CTL to a target cell the contents of the granules, including Granzyme B (GrB) and perforin, are released. GrB is the main effector of the granule-mediated cell death4,9.
GrB activity level is a good predictor of disease status in many viral infections and pathological conditions. Elevated levels of GrB were found in plasma of patients infected with EBV, HIV-1 and CMV7. Also, elevated GrB activity in virus-stimulated PBMC is a good predictor of influenza virus infection5. GrB seems to play a major role in tissue remodeling, cartilage degradation and inflammation. Significantly elevated GrB activity (10 pg/ml) was found in bronchalveolar lavage from patients with hypersensitivity pneumonitis as compared to negligible amounts found in normal subjects10. Furthermore, the number of GrB positive CTLs was elevated in serum and synovial fluid of RA patients and showed a direct correlation to severity of joint damage3,8.
GrB is neutral serine protease closely related structurally to chymotrypsin, with substrate specificity for aspartate at P1. It is synthesized as a zymogen, and it primarily expressed in cytotoxic cells, including CTLs, NK cells and large granular lymphocytes. Recent studies have detected active GrB in ovarian granulosa cells, and in malignant breast cancer cells1,2. NK cells constitutively express GrB, whereas in T lymphocytes, GrB expression is induced following exposure to antigen or following other types of stimulation. GrB enters the target cell through receptor-mediated endocytosis via the mannose 6-phosphate receptor. This requires the assistance of perforin, which is also released from the endosome. Once inside the cells, GrB initiates cell death through both caspase dependent and independent (mitochondrial) pathways (Fig. 1). Grb activates caspase 3 initiating the caspase cascade leading to apoptosis. GrB also cleaves BID resulting in a truncated form of BID called tBID, which along with Bax, is translocated to the mitochondria resulting in the release of cytochrome c and cell necrosis. This caspase-independent cell-death pathway is very important. It allows CTLs to kill virally infected cells in which caspases have been blocked by viral inhibitors, such as the cytokine response modifier A (crmA) expressed by poxviruses4,6. GrB has been used in ELISPOT assays as an indicator of CTL activity, but the assay does not measure GrB activity nor it can measure GrB levels in body fluids.
| | | | | | | Figure 1: GrB induces apoptosis via two distinct mechanisms | | | | | Antibodies
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| Anti-Granzyme B Mouse mAb (2C5/F5) |
IB, IP, NOT FS, NOT PS |
human, rat |
AM52 |
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| | | Assay Kits
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| InnoZyme™ Granzyme B Immunocapture Activity Assay Kit |
96-well plate |
96 Tests |
0.3 pg/ml (24 hour incubation) |
0.0625- 2 ng/ml (5 hour assay) and 3.125 - 50 pg/ml (24 hour assay) |
7 - 30 h |
Cell lysates, tissue extracts, and body fluids |
CBA014 |
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| | | Inhibitors
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| Caspase-8 Inhibitor II |
218759 |
| InSolution™ Caspase-8 Inhibitor II |
218840 |
| Caspase-8 Inhibitor I, Cell-Permeable |
218773 |
| Granzyme B Inhibitor I |
368050 |
| Granzyme B Inhibitor II |
368055 |
| Granzyme B Inhibitor IV |
368056 |
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| | | Peptides/Substrates
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| Granzyme B Substrate I, Colorimetric |
368057 |
| Granzyme B Substrate II, Fluorogenic |
368059 |
| Granzyme B Substrate VIII, Colorimetric |
368067 |
| Granzyme B Substrate IX, Fluorogenic |
368068 |
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| | | Proteins
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| Granzyme B, Human, Cell Culture-Derived |
368042 |
| Granzyme B, Human, Recombinant, E. coli |
368043 |
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| | | | | | Related Links | | Apoptosis Interactive Pathway | | Protease Assay Kits | | |
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