Regulation of IgE-dependent zinc release from human mast cells.
Int Arch Allergy Immunol
; 161 Suppl 2: 44-51, 2013.
Article
in En
| MEDLINE
| ID: mdl-23711853
ABSTRACT
BACKGROUND:
Zinc (Zn) affects many aspects of immune function, including thymic development and the activities of immune cells. Zn is also involved in many steps of high-affinity IgE receptor (FcεRI)-induced mast cell (MC) activation, which is required for degranulation and cytokine production. Intracellular Zn levels increase in mouse MCs after FcεRI stimulation. We previously reported that Zn distribution in a human MC line, LAD2, changed dramatically following FcεRI aggregation with synchrotron radiation microbeams. However, the kinetics of Zn distribution and the underlying mechanisms following FcεRI cross-linking remain unknown.METHODS:
We used cord-blood-derived MCs and LAD2 cells. Degranulation was assessed by ß-hexosaminidase (ß-hex) release. Extracellular Zn levels were determined by inductively coupled plasma atomic emission spectrometry or based on the fluorescence intensity of a Zn indicator. We also used RNAi to knockdown ZnT1 expression. mRNA expression levels were determined by real-time RT-PCR.RESULTS:
Zn was rapidly released from human MCs after FcεRI aggregation. The kinetics and optimal conditions for FcεRI cross-linking for Zn release were different from those for degranulation. Treating LAD2 cells with an intracellular Ca(2+) chelator significantly inhibited IgE-mediated ß-hex release but not Zn release. We investigated IgE-mediated ß-hex and Zn release with specific inhibitors of signaling pathways. Zn and ß-hex release were partly correlated with but also partly independent of IgE. Knockdown of the Zn efflux transporter, ZnT1, significantly inhibited Zn release from human MCs.CONCLUSIONS:
Our results indicate that IgE-dependent Zn release from human MCs involves signaling cascades that are distinct from those of degranulation. Thus, Zn may have a unique function as a mediator of allergic inflammation.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Zinc
/
Immunoglobulin E
/
Receptors, IgE
/
Mast Cells
Limits:
Humans
Language:
En
Journal:
Int Arch Allergy Immunol
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2013
Document type:
Article
Affiliation country: