Biology and clinical relevance of granulysin: REVIEW ARTICLE

Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4256, USA.
Tissue Antigens (Impact Factor: 2.14). 04/2009; 73(3):193-8. DOI: 10.1111/j.1399-0039.2008.01218.x
Source: PubMed


Granulysin is a cytolytic and proinflammatory molecule first identified by a screen for genes expressed 'late' (3-5 days) after activation of human peripheral blood mononuclear cells. Granulysin is present in cytolytic granules of cytotoxic T lymphocytes and natural killer cells. Granulysin is made in a 15-kDa form that is cleaved into a 9-kDa form at both the amino and the carboxy termini. The 15-kDa form is constitutively secreted, and its function remains poorly understood. The 9-kDa form is released by receptor-mediated granule exocytosis. Nine kiloDalton granulysin is broadly cytolytic against tumors and microbes, including gram-positive and gram-negative bacteria, fungi/yeast and parasites. It kills the causative agents of both tuberculosis and malaria. Granulysin is also a chemoattractant for T lymphocytes, monocytes and other inflammatory cells and activates the expression of a number of cytokines, including regulated upon activation T cell expressed and secreted (RANTES), monocyte chemoattractant protein (MCP)-1, MCP-3, macrophage inflammatory protein (MIP)-1 alpha, interleukin (IL)-10, IL-1, IL-6 and interferon (IFN)-alpha. Granulysin is implicated in a myriad of diseases including infection, cancer, transplantation, autoimmunity, skin and reproductive maladies. Small synthetic forms of granulysin are being developed as novel antibiotics. Studies of the full-length forms may give rise to new diagnostics and therapeutics for use in a wide variety of diseases.

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Available from: Alan M Krensky
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    • "Cytotoxic granules of humans and some other mammals, but not rodents, also contain a saposin-like pore-forming protein, granulysin (GNLY), which preferentially disrupts cholesterolpoor bacterial, fungal and parasite membranes (Krensky and Clayberger, 2009; Stenger et al., 1998). Incubation of extracellular bacteria, including mycobacteria, with GNLY is cytolytic, but only using micromolar GNLY concentrations or extremely hypotonic or acidic buffers (Ernst et al., 2000; Stenger et al., 1998), suggesting that GNLY acts mostly against bacteria within acidic phagosomes or may act with other agents. "
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