1. Mouse granzyme K has pro-inflammatory potential.
- Author
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Joeckel, L. T., Wallich, R., Martin, P., Sanchez-Martinez, D., Weber, F. C., Martin, S. F., Borner, C., Pardo, J., Froelich, C., and Simon, M. M.
- Subjects
INTERLEUKIN-1 ,ACUTE phase proteins ,KILLER cells ,LYMPHOCYTIC choriomeningitis virus ,ANTIGEN presenting cells - 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 P2X7 . 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. [ABSTRACT FROM AUTHOR]- Published
- 2011
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