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Mast cell stabilization improves survival by preventing apoptosis in sepsis.

Publication ,  Journal Article
Ramos, L; Peña, G; Cai, B; Deitch, EA; Ulloa, L
Published in: Journal of immunology (Baltimore, Md. : 1950)
July 2010

Inhibiting single cytokines produced modest effects in clinical trials, in part because the cytokines were not specific for sepsis, and sepsis may require cellular strategies. Previous studies reported that mast cells (MCs) fight infections in early sepsis. In this study, we report that MC stabilizers restrain serum TNF levels and improve survival in wild-type but not in MC-deficient mice. Yet, MC depletion in knockout mice attenuates serum TNF but does not improve survival in sepsis. Serum HMGB1 was the only factor correlating with survival. MC stabilizers inhibit systemic HMGB1 levels and rescue mice from established peritonitis. MC stabilizers fail to inhibit HMGB1 secretion from macrophages, but they prevent apoptosis and caspase-3 activation in sepsis. These results suggest that MC stabilization provides therapeutic benefits in sepsis by inhibiting extracellular release of HMGB1 from apoptotic cells. Our study provides the first evidence that MCs have major immunological implications regulating cell death in sepsis and represent a pharmacological target for infectious disorders in a clinically realistic time frame.

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Published In

Journal of immunology (Baltimore, Md. : 1950)

DOI

EISSN

1550-6606

ISSN

0022-1767

Publication Date

July 2010

Volume

185

Issue

1

Start / End Page

709 / 716

Related Subject Headings

  • Xanthones
  • Tumor Necrosis Factor-alpha
  • Thioxanthenes
  • Sepsis
  • Rats, Sprague-Dawley
  • Rats
  • Random Allocation
  • Organ Culture Techniques
  • Mice, Knockout
  • Mice, Inbred C57BL
 

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Ramos, L., Peña, G., Cai, B., Deitch, E. A., & Ulloa, L. (2010). Mast cell stabilization improves survival by preventing apoptosis in sepsis. Journal of Immunology (Baltimore, Md. : 1950), 185(1), 709–716. https://doi.org/10.4049/jimmunol.1000273
Ramos, Laura, Geber Peña, Bolin Cai, E. A. Deitch, and Luis Ulloa. “Mast cell stabilization improves survival by preventing apoptosis in sepsis.Journal of Immunology (Baltimore, Md. : 1950) 185, no. 1 (July 2010): 709–16. https://doi.org/10.4049/jimmunol.1000273.
Ramos L, Peña G, Cai B, Deitch EA, Ulloa L. Mast cell stabilization improves survival by preventing apoptosis in sepsis. Journal of immunology (Baltimore, Md : 1950). 2010 Jul;185(1):709–16.
Ramos, Laura, et al. “Mast cell stabilization improves survival by preventing apoptosis in sepsis.Journal of Immunology (Baltimore, Md. : 1950), vol. 185, no. 1, July 2010, pp. 709–16. Epmc, doi:10.4049/jimmunol.1000273.
Ramos L, Peña G, Cai B, Deitch EA, Ulloa L. Mast cell stabilization improves survival by preventing apoptosis in sepsis. Journal of immunology (Baltimore, Md : 1950). 2010 Jul;185(1):709–716.

Published In

Journal of immunology (Baltimore, Md. : 1950)

DOI

EISSN

1550-6606

ISSN

0022-1767

Publication Date

July 2010

Volume

185

Issue

1

Start / End Page

709 / 716

Related Subject Headings

  • Xanthones
  • Tumor Necrosis Factor-alpha
  • Thioxanthenes
  • Sepsis
  • Rats, Sprague-Dawley
  • Rats
  • Random Allocation
  • Organ Culture Techniques
  • Mice, Knockout
  • Mice, Inbred C57BL