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Cell Death Differ. 2011 Jul;18(7):1112-9. doi: 10.1038/cdd.2011.5. Epub 2011 Feb 11.

Mouse granzyme K has pro-inflammatory potential.

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1
Metschnikoff Laboratory, Max-Planck-Institut für Immunbiologie, Freiburg, Germany.

Abstract

Granzymes (gzms) are key components of T-killer (Tc) cells believed to mediate pro-apoptotic activities. Recent evidence suggests that gzms also possess non-cytotoxic activities that contribute to host defense. In this study, we show that Tc cells from lymphocytic choriomeningitis virus (LCMV)-infected wild-type (wt) and gzm A/B-deficient mice express similar levels of gzmK protein, with both mouse strains efficiently controlling infection. GzmK, in recombinant form or secreted by ex vivo-derived LCMV-immune gzmAxB(-/-) Tc cells, lacks pro-apoptotic activity. Instead, gzmK induces primary mouse macrophages to process and secrete interleukin-1β, independent of the ATP receptor P2X(7). Together with the finding that IL-1Ra (Anakinra) treatment inhibits virus elimination but not generation of cytotoxic Tc cells in wt mice, the data suggest that Tc cells control LCMV through non-cytotoxic processes that involve gzmK.

PMID:
21311565
PMCID:
PMC3131959
DOI:
10.1038/cdd.2011.5
[Indexed for MEDLINE]
Free PMC Article
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