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

Abstract

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-1α) 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-1α. This effect was not due to reduced protein induction but resulted from heightened intracellular accumulation of MIP-1α, 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.

• Authors: N Baschuk, N Wang, S V Watt, H Halse, C House, P I Bird, R Strugnell, J A Trapani, M J Smyth, D M Andrews
• Journal: Cell death & disease (Cell Death Dis) Vol. 5 Pg. e1115 (Mar 13 2014) ISSN: 2041-4889 [Electronic] England
• PMID: 24625974 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CCL3 protein, human
• Ccl3 protein, mouse
• Chemokine CCL3
• Interleukins
• GZMM protein, human
• Granzymes
• Gzmb protein, mouse
• Gzmm protein, mouse

Topics

• Animals
• Cells, Cultured
• Chemokine CCL3 (metabolism)
• Chemotaxis, Leukocyte
• Coculture Techniques
• Disease Models, Animal
• Granzymes (deficiency, genetics, metabolism)
• Humans
• Immunity, Innate
• Interleukins (metabolism)
• Killer Cells, Natural (enzymology, immunology, microbiology)
• Listeria monocytogenes (immunology, pathogenicity)
• Listeriosis (enzymology, genetics, immunology, microbiology)
• Mice
• Mice, Knockout
• Time Factors