The Regulation of Liver Cell Survival by Complement

Complement effectors are known to contribute to host cell injury in several inflammatory diseases. Contrary to this paradigm, in this study utilizing surgical liver resection (partial hepatectomy) in various complement-deficient mice as a model, we have demonstrated that complement anaphylatoxins C3...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2009-05, Vol.182 (9), p.5412-5418
Main Authors: Markiewski, Maciej M, DeAngelis, Robert A, Strey, Christoph W, Foukas, Periklis G, Gerard, Craig, Gerard, Norma, Wetsel, Rick A, Lambris, John D
Format: Article
Language:English
Subjects:
Animals
Cell Death - genetics
Cell Death - immunology
Cell Survival - genetics
Cell Survival - immunology
Complement Activation - genetics
Complement Activation - immunology
Complement C3 - deficiency
Complement C3 - genetics
Complement C3 - physiology
Complement C3a - deficiency
Complement C3a - genetics
Complement C3a - physiology
Complement C5a - deficiency
Complement C5a - genetics
Complement C5a - physiology
Complement System Proteins - deficiency
Complement System Proteins - genetics
Complement System Proteins - physiology
Hepatectomy
Liver - cytology
Liver - immunology
Liver Regeneration - genetics
Liver Regeneration - immunology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
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Summary:Complement effectors are known to contribute to host cell injury in several inflammatory diseases. Contrary to this paradigm, in this study utilizing surgical liver resection (partial hepatectomy) in various complement-deficient mice as a model, we have demonstrated that complement anaphylatoxins C3a and C5a are required for the survival of liver cells during regeneration. The mechanisms of these cytoprotective functions of complement were related to the regulation of IL-6 and TNF production or release after liver resection. Disturbances in the cytokine milieu, induced by a loss of complement activity, were found to alter prosurvival signaling, including the IL-6/STAT3 and PI3K/Akt/mammalian target of rapamycin pathways. In conclusion, this study documents functions of complement proteins as prosurvival factors that, through their interactions with cytokines, inhibit apoptotic signaling in proliferating cells of epithelial origin.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.0804179