TY - JOUR
T1 - Mast cells promote homeostasis by limiting endothelin-1-induced toxicity
AU - Maurer, Marcus
AU - Wedemeyer, Jochen
AU - Metz, Martin
AU - Piliponsky, Adrian M.
AU - Weller, Karsten
AU - Chatterjea, Devavani
AU - Clouthier, David E.
AU - Yanagisawa, Masashi M.
AU - Tsai, Mindy
AU - Galli, Stephen J.
N1 - Funding Information:
Acknowledgements We thank R. Parker of the Biometrics Center of the Beth Israel Deaconess Medical Center for consultation regarding the statistical analysis of the data, S. Fish, L. Fox, M. Liebersbach and A. Xu for technical assistance, M.-H. Jouvin for discussions and critical reading of the manuscript, and R. Paus for supporting M. Metz. This work was supported by United States Public Health Science Grants (to S.J.G.), by grants of the Deutsche Forschungsgemeinschaft (to M. Maurer, J.W. and M. Metz), and by a grant of the Boehringer Ingelheim Fonds (to M. Metz).
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2004/11/25
Y1 - 2004/11/25
N2 - 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.
AB - 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.
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U2 - 10.1038/nature03085
DO - 10.1038/nature03085
M3 - Article
C2 - 15543132
AN - SCOPUS:9644269070
SN - 0028-0836
VL - 432
SP - 512
EP - 516
JO - Nature
JF - Nature
IS - 7016
ER -