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Publication : NK cell intrinsic regulation of MIP-1α by granzyme M.

First Author  Baschuk N Year  2014
Journal  Cell Death Dis Volume  5
Pages  e1115 PubMed ID  24625974
Mgi Jnum  J:302261 Mgi Id  MGI:6507973
Doi  10.1038/cddis.2014.74 Citation  Baschuk N, et al. (2014) NK cell intrinsic regulation of MIP-1alpha by granzyme M. Cell Death Dis 5:e1115
abstractText  Granzymes are generally recognized for their capacity to induce various pathways of perforin-dependent target cell death. Within this serine protease family, Granzyme M (GrzM) is unique owing to its preferential expression in innate effectors such as natural killer (NK) cells. During Listeria monocytogenes infection, we observed markedly reduced secretion of macrophage inflammatory protein-1 alpha (MIP-1alpha) in livers of GrzM-deficient mice, which resulted in significantly impaired NK cell recruitment. Direct stimulation with IL-12 and IL-15 demonstrated that GrzM was required for maximal secretion of active MIP-1alpha. This effect was not due to reduced protein induction but resulted from heightened intracellular accumulation of MIP-1alpha, with reduced release. These results demonstrate that GrzM is a critical mediator of innate immunity that can regulate chemotactic networks and has an important role in the initiation of immune responses and pathogen control.
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