Polydatin (PD) inhibits IgE-mediated passive cutaneous anaphylaxis in mice by stabilizing mast cells through modulating Ca{sup 2+} mobilization

Journal Article · Thu Nov 01 04:00:00 EDT 2012 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/J.TAAP.2012.08.024· OSTI ID:22215967

Yuan, Meichun ^[1]; Li, Jianjie ^[2]; Lv, Jingzhang ^[3]; Mo, Xucheng; Yang, Chengbin ^[2]; Chen, Xiangdong ^[1]; Liu, Zhigang ^[2]; Liu, Jie ^[1]

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1. Department of Pathophysiology, School of Medicine, Shenzhen University, Shenzhen 518060 (China)
2. State Key Laboratory of Respiratory Disease for Allergy at Shengzhen University, Shenzhen 518060 (China)
3. Shenzhen Entry-Exit Inspection and Quarantine Bureau, Shenzhen 518045 (China)

Mast cells play a key role in the pathogenesis of asthma and are a promising target for therapeutic intervention in asthma. This study investigated the effects of polydatin (PD), a resveratrol glucoside, on mast cell degranulation upon cross-linking of the high-affinity IgE receptors (FcεRI), as well as the anti-allergic activity of PD in vivo. Herein, we demonstrated that PD treatment for 30 min suppressed FcεRI-mediated mast cell degranulation in a dose-dependent manner. Concomitantly, PD significantly decreased FcεRI-mediated Ca{sup 2+} increase in mast cells. The suppressive effects of PD on FcεRI-mediated Ca{sup 2+} increase were largely inhibited by using LaCl{sub 3} to block the Ca{sup 2+} release-activated Ca{sup 2+} channels (CRACs). Furthermore, PD significantly inhibited Ca{sup 2+} entry through CRACs evoked by thapsigargin (TG). Knocking down protein expression of Orai1, the pore-forming subunit of CRACs, significantly decreased PD suppression of FcεRI-induced intracellular Ca{sup 2+} influx and mast cell degranulation. In a mouse model of mast cell-dependent passive cutaneous anaphylaxis (PCA), in vivo PD administration suppressed mast cell degranulation and inhibited anaphylaxis. Taken together, our data indicate that PD stabilizes mast cells by suppressing FcεRI-induced Ca{sup 2+} mobilization mainly through inhibiting Ca{sup 2+} entry via CRACs, thus exerting a protective effect against PCA. -- Highlights: ► Polydatin can prevent the pathogenesis of passive cutaneous anaphylaxis in mice. ► Polydatin stabilizes mast cells by decreasing FcεRI-mediated degranulation. ► Polydatin suppresses Ca{sup 2+} entry through CRAC channels in mast cells.

• OSTI ID: 22215967
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 3 Vol. 264; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANAPHYLAXIS
ASTHMA
BROMIDES
CALCIUM
CROSS-LINKING
ENDOPLASMIC RETICULUM
IN VIVO
LANTHANUM CHLORIDES
MAST CELLS
MICE
OXYGEN
PATHOGENESIS
RECEPTORS