The novel H2S donor 4‐carboxy‐phenyl isothiocyanate inhibits mast cell degranulation and renin release by decreasing intracellular calcium

Background and Purpose Hydrogen sulfide (H2S) modulates many pathophysiological processes, including inflammation and allergic reactions, in which mast cells act as major effector cells. IgE receptor (FcεRI) cross linking leads to an increase in intracellular calcium ([Ca+2]i), a critical step in ma...

Full description

Saved in:
Bibliographic Details
Published in:British journal of pharmacology 2016-11, Vol.173 (22), p.3222-3234
Main Authors: Marino, Alice, Martelli, Alma, Citi, Valentina, Fu, Ming, Wang, Rui, Calderone, Vincenzo, Levi, Roberto
Format: Article
Language:English
Subjects:
Antigens
Calcium
Calcium (intracellular)
Calcium ions
Cell activation
Cell lines
Degranulation
Effector cells
Hydrogen sulfide
Hypersensitivity
Immunoglobulin E
Intracellular
Isothiocyanate
Mast cells
Phosphorylation
Proteins
Renin
Research Paper
Research Papers
Rodents
Syk protein
Thapsigargin
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Background and Purpose Hydrogen sulfide (H2S) modulates many pathophysiological processes, including inflammation and allergic reactions, in which mast cells act as major effector cells. IgE receptor (FcεRI) cross linking leads to an increase in intracellular calcium ([Ca+2]i), a critical step in mast cell degranulation. The aim of this study was to investigate the role of H2S in [Ca+2]i‐dependent mast cell activation. Experimental Approach We investigated the effects of H2S, either endogenously produced or released by the slow H2S donor 4‐carboxy‐phenyl isothiocyanate (PhNCS‐COOH), on antigenic‐ and non‐antigenic degranulation of native murine mast cells, and human and rat (RBL‐2H3) mast cell lines. We measured the release of specific mast cell degranulation markers (β‐hexosaminidase and renin), as well as changes in [Ca+2]i and phosphorylation of proteins downstream of FcεRI activation. Key Results Endogenously produced H2S inhibited antigen‐induced degranulation in RBL‐2H3. Similarly, H2S released by PhNCS‐COOH (10–300 μM) reduced, in a concentration‐dependent manner, antigenic and non‐antigenic degranulation and renin release in all mast cell types. Notably, PhNCS‐COOH also prevented in a concentration‐dependent mode the increase in [Ca+2]i elicited by Ca+2 ionophore, thapsigargin and FcεRI activation. Moreover, PhNCS‐COOH attenuated the phosphorylation of Syk, cPLA‐2 and PLCγ1 in antigen‐stimulated RBL‐2H3 cells. Conclusion and Implications Collectively, our results demonstrate that, by attenuating the phosphorylation of proteins downstream of FcεRI cross‐linking on mast cells, H2S diminishes [Ca+2]i availability and thus mast cell degranulation and renin release. These findings suggest that PhNCS‐COOH could be a strategic therapeutic tool in mast cell‐mediated allergic conditions.
ISSN:0007-1188
1476-5381
DOI:10.1111/bph.13583