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Mast cells promote homeostasis by limiting endothelin-1-induced toxicity
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 ET(A)-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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“One step in that direction was the finding that ET-1 can initiate a homeostatic mechanism whereby proteases released by mast cells activated by ET-1 can degrade that vasoactive peptide and thereby diminish its potential toxicity in vivo [65].”
From Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy (2020) · cites this paper as [65]
In the citing paper
“Using mast cell knock-in C57BL/6-KitW-sh/KitW-sh mice engrafted with ETA receptor-deficient or WT mast cells derived in vitro from ETA−/− or ETA−/+ embryonic stem cells, Maurer et al. found that mast cell activation by ET-1 via the ETA receptor contributed to this effect [65].”
From Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy (2020) · cites this paper as [65]
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Self-citationDavenport, A. P., Hyndman, K. A., Dhaun, N., Southan, C., Kohan, D. E., Pollock, J. S., Pollock, D. M., Webb, D. J., & Maguire, J. J. (2016) · Pharmacological Reviews · doi:10.1124/pr.115.011833 · Cited by 772
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Metadata
- Authors
- Maurer, M., Wedemeyer, J., Metz, M., Piliponsky, A. M., Weller, K., Chatterjea, D., Clouthier, D. E., Yanagisawa, M. M., Tsai, M., & Galli, S. J.
- Venue
- Nature
- Published
- 2004-11
- Volume
- 432
- Issue
- 7016
- Pages
- 512-516
- ISSN
- 0028-0836
- 1476-4687
- Cited by
- 258
- References
- 0
- Language
- en
- Licence
- www.springer.com/tdm (tdm)
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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. https://doi.org/10.1038/nature03085