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논문검색

PP-35

PKC-mediated N-glycosylation of NOX2 regulates its trafficking to the lipid rafts and ROS-dependent degranulation in human mast cells stimulated with protozoan parasite Trichomonas vaginalis-derived secretory products.

초록

영어

Degranulation in human mast cells contributes to provocation of allergic inflammation and innate immunity to parasites. Trichomonas vaginalis is transmitted by sexual intercourse and causes the acute and chronic allergic inflammation. Although a recent report has shown that mast cells are degranulated in response to T. vaginalis-derived secretory products (TvSP), detailed signaling mechanisms of TvSP- induced mast cell degranulation are not fully understood. We report that N-glycosylation of NOX2 play an important role in surface trafficking of NOX2, which can regulate ROS-dependent degranulation in TvSP- stimulated human mast cells. Stimulation with TvSPinduced NOX2 activation such as p47phox phosphorylation and NOX2 glycosylation, production of intracellular ROS, and release of granular proteins such as histamine and -hexosaminidase via BLT1. Inhibition of ROS generation with NOX2 inhibitors also reduced TvSP-triggered degranulation. Moreover, TvSP promoted trafficking of intracellular NOX2 to the cell surface in a BLT1-dependent manner. Such BLT1-mediated surface migration of NOX2 was dependent upon N-glycosyation status of NOX2. Inhibiting N-glycosylation of NOX2 by N-glycosylation inhibitor tunicamycin reduced surface trafficking of NOX2, ROS generation, and degranulation induced by TvSP. PKC inhibitor prevented TvSP-triggered glycosylation of NOX2, its surface trafficking, ROS generation, degranulation. Finally, disruption of lipid rafts with M □CD prevented glycosylation-dependent surface trafficking of NOX2, ROS generation, and degranulation. These results suggest that PKC-mediated N- glycosylation regulates its trafficking of NOX2 to the lipid rafts, which is required for ROS-dependent degranulation in mast cells induced by T. vaginalis-derived secretory products.

저자정보

  • Arim Min Department of Environmental Medical Biology, Institute of Tropical Medicine, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea
  • Young Hee Nam Department of Environmental Medical Biology, Institute of Tropical Medicine
  • Young-Ah Lee Department of Environmental Medical Biology, Institute of Tropical Medicine
  • Kyoung-Ju Song Department of Environmental Medical Biology, Institute of Tropical Medicine
  • Myeong Heon Shin Department of Environmental Medical Biology, Institute of Tropical Medicine

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