Mast cells promote homeostasis by limiting endothelin-1-induced toxicity

Marcus Maurer, Jochen Wedemeyer, Martin Metz, Adrian M. Piliponsky, Karsten Weller, Devavani Chatterjea, David E. Clouthier, Masashi M. Yanagisawa, Mindy Tsai, Stephen J. Galli

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233 Scopus citations

Abstract

Endothelin-1 (ET-1) is a 21-amino-acid peptide, derived from vascular endothelial cells, with potent vasoconstrictor activity. ET-1 has been implicated in diverse physiological or pathological processes, including the vascular changes associated with sepsis. However, the factors that regulate ET-1-associated toxicity during bacterial infections, or in other settings, are not fully understood. Both the pathology associated with certain allergic and autoimmune disorders, and optimal host defence against bacterial and parasitic infections are mediated by mast cells. In vitro, mast cells can produce ET-1 (ref. 11), undergo ET-1-dependent and endothelin-A receptor (ET A)-dependent activation, and release proteases that degrade ET-1 (ref. 14). Although the potential relationships between mast cells and the ET-1 system thus may be complex, the importance of interactions between ET-1 and mast cells in vivo is obscure. Here we show that ETA-dependent mast-cell activation can diminish both ET-1 levels and ET-1-induced pathology in vivo, and also can contribute to optimal survival during acute bacterial peritonitis. These findings identify a new biological function for mast cells: promotion of homeostasis by limiting the toxicity associated with an endogenous mediator.

Original languageEnglish (US)
Pages (from-to)512-516
Number of pages5
JournalNature
Volume432
Issue number7016
DOIs
StatePublished - Nov 25 2004

ASJC Scopus subject areas

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    Maurer, M., Wedemeyer, J., Metz, M., Piliponsky, A. M., Weller, K., Chatterjea, D., Clouthier, D. E., Yanagisawa, M. M., Tsai, M., & Galli, S. J. (2004). Mast cells promote homeostasis by limiting endothelin-1-induced toxicity. Nature, 432(7016), 512-516. https://doi.org/10.1038/nature03085