Article (Scientific journals)
Different activation signals induce distinct mast cell degranulation strategies.
Gaudenzio, Nicolas; Sibilano, Riccardo; Marichal, Thomas et al.
2016In Journal of Clinical Investigation, 126 (10), p. 3981-3998
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Abstract :
[en] Mast cells (MCs) influence intercellular communication during inflammation by secreting cytoplasmic granules that contain diverse mediators. Here, we have demonstrated that MCs decode different activation stimuli into spatially and temporally distinct patterns of granule secretion. Certain signals, including substance P, the complement anaphylatoxins C3a and C5a, and endothelin 1, induced human MCs rapidly to secrete small and relatively spherical granule structures, a pattern consistent with the secretion of individual granules. Conversely, activating MCs with anti-IgE increased the time partition between signaling and secretion, which was associated with a period of sustained elevation of intracellular calcium and formation of larger and more heterogeneously shaped granule structures that underwent prolonged exteriorization. Pharmacological inhibition of IKK-beta during IgE-dependent stimulation strongly reduced the time partition between signaling and secretion, inhibited SNAP23/STX4 complex formation, and switched the degranulation pattern into one that resembled degranulation induced by substance P. IgE-dependent and substance P-dependent activation in vivo also induced different patterns of mouse MC degranulation that were associated with distinct local and systemic pathophysiological responses. These findings show that cytoplasmic granule secretion from MCs that occurs in response to different activating stimuli can exhibit distinct dynamics and features that are associated with distinct patterns of MC-dependent inflammation.
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Gaudenzio, Nicolas
Sibilano, Riccardo
Marichal, Thomas  ;  Université de Liège > Département des sciences fonctionnelles (DSF) > GIGA-R : Biochimie et biologie moléculaire
Starkl, Philipp
Reber, Laurent L.
Cenac, Nicolas
McNeil, Benjamin D.
Dong, Xinzhong
Hernandez, Joseph D.
Sagi-Eisenberg, Ronit
Hammel, Ilan
Roers, Axel
Valitutti, Salvatore
Tsai, Mindy
Espinosa, Eric
Galli, Stephen J.
More authors (6 more) Less
Language :
English
Title :
Different activation signals induce distinct mast cell degranulation strategies.
Publication date :
2016
Journal title :
Journal of Clinical Investigation
ISSN :
0021-9738
eISSN :
1558-8238
Publisher :
American Society for Clinical Investigation, United States - Michigan
Volume :
126
Issue :
10
Pages :
3981-3998
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 18 January 2017

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