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Article Dans Une Revue Journal of Clinical Investigation Année : 2016

Different activation signals induce distinct mast cell degranulation strategies

Nicolas Cenac
Ronit Sagi-Eisenberg
  • Fonction : Auteur
Eric Espinosa

Résumé

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-β 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.

Dates et versions

hal-03532419 , version 1 (18-01-2022)

Identifiants

Citer

Nicolas Gaudenzio, Riccardo Sibilano, Thomas Marichal, Philipp Starkl, Laurent Reber, et al.. Different activation signals induce distinct mast cell degranulation strategies. Journal of Clinical Investigation, 2016, 126 (10), pp.3981-3998. ⟨10.1172/JCI85538⟩. ⟨hal-03532419⟩
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