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https://hdl.handle.net/2440/61299
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Type: | Journal article |
Title: | Mast cell-derived TNF can exacerbate mortality during severe bacterial infections in C57BL/6-KitW-sh/W-sh mice |
Author: | Piliponsky, A. Chen, C. Grimbaldeston, M. Burns-Guydish, S. Hardy, J. Kalesnikoff, J. Contag, C. Tsai, M. Galli, S. |
Citation: | American Journal of Pathology, 2010; 176(2):926-938 |
Publisher: | Amer Soc Investigative Pathology Inc |
Issue Date: | 2010 |
ISSN: | 0002-9440 1525-2191 |
Statement of Responsibility: | Adrian M. Piliponsky, Ching-Cheng Chen, Michele A. Grimbaldeston, Stacy M. Burns-Guydish, Jonathan Hardy, Janet Kalesnikoff, Christopher H. Contag, Mindy Tsai and Stephen J. Galli |
Abstract: | We used mast cell-engrafted genetically mast cell-deficient C57BL/6-Kit(W-sh/W-sh) mice to investigate the roles of mast cells and mast cell-derived tumor necrosis factor in two models of severe bacterial infection. In these mice, we confirmed findings derived from studies of mast cell-deficient WBB6F(1)-Kit(W/W-v) mice indicating that mast cells can promote survival in cecal ligation and puncture (CLP) of moderate severity. However, we found that the beneficial role of mast cells in this setting can occur independently of mast cell-derived tumor necrosis factor. By contrast, using mast cell-engrafted C57BL/6-Kit(W-sh/W-sh) mice, we found that mast cell-derived tumor necrosis factor can increase mortality during severe CLP and can also enhance bacterial growth and hasten death after intraperitoneal inoculation of Salmonella typhimurium. In WBB6F(1)-Kit(W-sh/W-sh) mice, mast cells enhanced survival during moderately severe CLP but did not significantly change the survival observed in severe CLP. Our findings in three types of genetically mast cell-deficient mice thus support the hypothesis that, depending on the circumstances (including mouse strain background, the nature of the mutation resulting in a mast cell deficiency, and type and severity of infection), mast cells can have either no detectable effect or opposite effects on survival during bacterial infections, eg, promoting survival during moderately severe CLP associated with low mortality but, in C57BL/6-Kit(W-sh/W-sh) mice, increasing mortality during severe CLP or infection with S. typhimurium. |
Keywords: | Mast Cells Animals Mice, Congenic Mice, Inbred C3H Mice, Inbred C57BL Mice, Transgenic Mice Salmonella typhimurium Bacterial Infections Salmonella Infections, Animal Disease Progression Tumor Necrosis Factor-alpha Immunotherapy, Adoptive Severity of Illness Index Female Proto-Oncogene Proteins c-kit |
Rights: | Copyright © 2010 by the American Society for Investigative Pathology. |
DOI: | 10.2353/ajpath.2010.090342 |
Published version: | http://dx.doi.org/10.2353/ajpath.2010.090342 |
Appears in Collections: | Aurora harvest 5 Molecular and Biomedical Science publications |
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