Granzyme
Granzymes are
In addition to killing their target cells, granzymes can target and kill intracellular pathogens. Granzymes A and B induce lethal oxidative damage in bacteria by cleaving components of the electron transport chain,[2] while granzyme B cleaves viral proteins to inhibit viral activation and replication.[5] The granzymes bind directly to the nucleic acids DNA and RNA; this enhances their cleavage of nucleic acid binding proteins.[4]
More recently, in addition to T lymphocytes, granzymes have been shown to be expressed in other types of immune cells such as dendritic cells, B cells and mast cells. In addition, granzymes may also be expressed in non-immune cells such as keratinocytes, pneumocytes and chondrocytes.[6] As many of these cell types either do not express perforin or do not form immunological synapses, granzyme B is released extracellularly. Extracellular granzyme B can accumulate in the extracellular space in diseases associated with dysregulated or chronic inflammation leading to the degradation of extracellular matrix proteins and impaired tissue healing and remodelling.[7] Extracellular granzyme B has been implicated in the pathogenesis of atherosclerosis,[8] aneurysm,[9][10] vascular leakage,[11] chronic wound healing,[10][12] and skin aging.[13]
History
In 1986 Jürg Tschopp and his group published a paper on their discovery of granzymes. In the paper they discussed how they purified, characterized and discovered a variety of granzymes found within cytolytic granules that were carried by cytotoxic T lymphocytes and natural killer cells. Jürg was able to identify 8 different granzymes and discovered partial amino acid sequences for each. The molecules were unofficially named Grs for five years before Jürg and his team came up with the name granzymes which was widely accepted by the scientific community.[14]
Granzyme secretion can be detected and measured using
Other functions
In Cullen's paper “Granzymes in Cancer and Immunity” he discusses how
Cullen further states in his paper that granzymes may have a role in immunomodulation, or the job of maintaining homeostasis in the immune system during an infection. “In humans, loss of perforin function leads to a syndrome called familial hemophagocytic lymphohistiocytosis […]”.[15] This syndrome can lead to death because both T cells and macrophages multiply to fight the pathogen, resulting in harmful levels of proinflammatory cytokines. The overactivation can lead to inflammation of vital organs, anemia via overactivated macrophages phagocytosing blood cells, and can potentially be fatal.
In Trapani's paper he talks about how granzymes may have other functions, in addition to their ability to fight off infection. Granzyme A contains certain chemicals that allow it to cause proliferation in B cells to reduce the chance of cancer growth and formation. Test on mice have shown that granzyme A and B might not have a direct link to controlling viral infections, but helping accelerate the immune systems response.[16]
In cancer research
In Cullen's paper “Granzymes in Cancer and Immunity” he describes the process of “
Tumors have the ability to escape from immune surveillance by secreting immunosuppressive
Perforin's role in protecting the body against lymphoma was emphasized when scientists discovered that p53 did not have as big of a role in lymphoma surveillance as its counterpart perforin. Perforin and granzymes have been found to have a directly related ability to protect the body against the formation of different kinds of lymphomas.[15]