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SNAP23-Dependent Surface Translocation of Leukotriene B4 (LTB4) Receptor 1 Is Essential for NOX2-Mediated Exocytotic Degranulation in Human Mast Cells Induced by Trichomonas vaginalis-Secreted LTB4

 Arim Min  ;  Young Ah Lee  ;  Kyeong Ah Kim  ;  Jamel El-Benna  ;  Myeong Heon Shin 
 INFECTION AND IMMUNITY, Vol.85(1) : 00526-16, 2017 
Journal Title
Issue Date
Cell Line ; Cell Membrane/metabolism ; Exocytosis/physiology* ; Female ; Humans ; Inflammation/metabolism ; Inflammation/microbiology ; Leukotriene B4/metabolism* ; Mast Cells ; Membrane Glycoproteins/metabolism* ; NADPH Oxidase 2 ; NADPH Oxidases/metabolism* ; Protein Transport/physiology* ; Qb-SNARE Proteins/metabolism* ; Qc-SNARE Proteins/metabolism* ; RNA, Small Interfering/metabolism ; Reactive Oxygen Species/metabolism ; Receptors, Leukotriene B4/metabolism* ; Signal Transduction ; Trichomonas Vaginitis/parasitology ; Trichomonas vaginalis/metabolism*
BLT1 ; LTB4 ; NOX2 ; SNAP23 ; Trichomonas vaginalis ; exocytotic degranulation ; human mast cells ; surface trafficking
Trichomonas vaginalis is a sexually transmitted parasite that causes vaginitis in women and itself secretes lipid mediator leukotriene B4 (LTB4). Mast cells are important effector cells of tissue inflammation during infection with parasites. Membrane-bridging SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complexes are critical for fusion during exocytosis. Although T. vaginalis-derived secretory products (TvSP) have been shown to induce exocytosis in mast cells, information regarding the signaling mechanisms between mast cell activation and TvSP is limited. In this study, we found that SNAP23-dependent surface trafficking of LTB4 receptor 1 (BLT1) is required for nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2)-mediated exocytotic degranulation of mast cells induced by TvSP. First, stimulation with TvSP induced exocytotic degranulation and reactive oxygen species (ROS) generation in HMC-1 cells. Next, TvSP-induced ROS generation and exocytosis were strongly inhibited by transfection of BLT1 small interfering RNA (siRNA). TvSP induced trafficking of BLT1 from the cytosol to the plasma membrane. We also found that knockdown of SNAP23 abrogated TvSP-induced ROS generation, exocytosis, and surface trafficking of BLT1 in HMC-1 cells. By coimmunoprecipitation, there was a physical interaction between BLT1 and SNAP23 in TvSP-stimulated HMC-1 cells. Taken together, our results suggest that SNAP23-dependent surface trafficking of BLT1 is essential for exocytosis in human mast cells induced by T. vaginalis-secreted LTB4 Our data collectively demonstrate a novel regulatory mechanism for SNAP23-dependent mast cell activation of T. vaginalis-secreted LTB4 involving surface trafficking of BLT1. These results can help to explain how the cross talk mechanism between parasite and host can govern deliberately tissue inflammatory responses.
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1. College of Medicine (의과대학) > Dept. of Tropica Medicine (열대의학교실) > 1. Journal Papers
Yonsei Authors
Min, A Rim(민아림) ORCID logo https://orcid.org/0000-0003-2938-9630
Shin, Myeong Heon(신명헌) ORCID logo https://orcid.org/0000-0001-8207-6110
Lee, Young Ah(이영아) ORCID logo https://orcid.org/0000-0002-0414-842X
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