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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
Statement of
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
Mice, Congenic
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Transgenic
Salmonella typhimurium
Bacterial Infections
Salmonella Infections, Animal
Disease Progression
Tumor Necrosis Factor-alpha
Immunotherapy, Adoptive
Severity of Illness Index
Proto-Oncogene Proteins c-kit
Rights: Copyright © 2010 by the American Society for Investigative Pathology.
DOI: 10.2353/ajpath.2010.090342
Appears in Collections:Aurora harvest 5
Molecular and Biomedical Science publications

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