title: 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.
abstract: 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 LTB4receptor 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 LTB4Our data collectively demonstrate a novel regulatory mechanism for SNAP23-dependent mast cell activation of T. vaginalis-secreted LTB4involving 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.
authors: Department of Environmental Medical Biology, Institute of Tropical Medicine, Yonsei University College of Medicine, Seoul, South Korea.
authors: Arim
authors: http://orcid.org/0000-0003-2938-9630
authors: A
authors: Min
authors: Department of Environmental Medical Biology, Institute of Tropical Medicine, Yonsei University College of Medicine, Seoul, South Korea.
authors: Young Ah
authors: YA
authors: Lee
authors: Department of Environmental Medical Biology, Institute of Tropical Medicine, Yonsei University College of Medicine, Seoul, South Korea.
authors: Kyeong Ah
authors: KA
authors: Kim
authors: INSERM U1149, CNRS-ERL8252, Centre de Recherche sur l'Inflammation, Laboratoire d'Excellence Inflamex, Université Paris-Diderot, Sorbonne Paris Cité, Faculté de Médecine Xavier Bichat, Paris, France.
authors: Jamel
authors: J
authors: El-Benna
authors: Department of Environmental Medical Biology, Institute of Tropical Medicine, Yonsei University College of Medicine, Seoul, South Korea myeong@yuhs.ac.
authors: Myeong Heon
authors: MH
authors: Shin
mesh_terms: D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D005089:Exocytosis / Q000502:physiology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000382:microbiology; D007975:Leukotriene B4 / Q000378:metabolism*; D008407:Mast Cells; D008562:Membrane Glycoproteins / Q000378:metabolism*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology*; D050766:Qb-SNARE Proteins / Q000378:metabolism*; D050767:Qc-SNARE Proteins / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D018102:Receptors, Leukotriene B4 / Q000378:metabolism*; D015398:Signal Transduction; D014247:Trichomonas Vaginitis / Q000469:parasitology; D014246:Trichomonas vaginalis / Q000378:metabolism*
chemical_list: C513240:LTB4R protein, human; D008562:Membrane Glycoproteins; D050766:Qb-SNARE Proteins; D050767:Qc-SNARE Proteins; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D018102:Receptors, Leukotriene B4; C100493:SNAP23 protein, human; D007975:Leukotriene B4; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases
keywords: BLT1; LTB4; NOX2; SNAP23; Trichomonas vaginalis; exocytotic degranulation; human mast cells; surface trafficking