Down-regulation of intracellular vesicle trafficking by the treatment of zoledronate in mast cells

抄録

Background Zoledronate is widely used in the treatments of osteoporosis and cancer-related bone disorders. Zoledronate also modulates immunity as results of inhibition of the mevalonate pathway. Our study is undertaken to investigate the effects of zoledronate on antigen-dependent activity in mast cells.

Methods Non-treated RBL-2H3 cells and zoledronate-treated mast cells were sensitized using specific anti-DNP-BSA IgE and stimulated by DNP-BSA. Histamine released from mast cells. , a hallmark of mast cell activity, was measured. The exocytotic process in mast cells was screened using a high-throughput quantification system and the trajectory of single functional vesicles was monitored. The possible interactive networks of vesicle-associated proteins were elucidated.

Results Zoledronate inhibits the antigen-dependent histamine release from mast cells. The results of high-throughput quantification screening suggest that the exocytotic process were down-regulated in zoledronate-treated mast cells. Zoledronate detains the velocity of vesicle trafficking and blocks membrane fusion of exocytotic vesicle. Finally, zoledronate suppresses the formations of myosin Va/Rab3a complex and syntaxin4/VAMP7 complex in antigen-activitied mast cells.

Conclusions Our finding imply that zoledronate down-regulates the antigen-dependent mast cell activity via disturbing the intracellular vesicle trafficking.