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AhYoung, Andrew P.; Eckard, Sterling C.; Gogineni, Alvin; Xi, Hongkang; Lin, S. Jack; Gerhardy, Stefan; Cox, Christian; Phung, Qui T.; Hackney, Jason A.; Katakam, Anand Kumar; Reichelt, Mike; Caplazi, Patrick; Manzanillo, Paolo; Zhang, Juan; Roose-Girma, Merone; Tam, Lucinda W.; Newman, Robert J.; Murthy, Aditya; Weimer, Robby M.; Lill, Jennie R.; Lee, Wyne P.; Grimbaldeston, Michele; Kirchhofer, Daniel; van Lookeren Campagne, Menno

Neutrophil serine protease 4 is required for mast cell-dependent vascular leakage

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  • Medientyp: E-Artikel
  • Titel: Neutrophil serine protease 4 is required for mast cell-dependent vascular leakage
  • Beteiligte: AhYoung, Andrew P.; Eckard, Sterling C.; Gogineni, Alvin; Xi, Hongkang; Lin, S. Jack; Gerhardy, Stefan; Cox, Christian; Phung, Qui T.; Hackney, Jason A.; Katakam, Anand Kumar; Reichelt, Mike; Caplazi, Patrick; Manzanillo, Paolo; Zhang, Juan; Roose-Girma, Merone; Tam, Lucinda W.; Newman, Robert J.; Murthy, Aditya; Weimer, Robby M.; Lill, Jennie R.; Lee, Wyne P.; Grimbaldeston, Michele; Kirchhofer, Daniel; van Lookeren Campagne, Menno
  • Erschienen: Springer Science and Business Media LLC, 2020
  • Erschienen in: Communications Biology
  • Sprache: Englisch
  • DOI: 10.1038/s42003-020-01407-0
  • ISSN: 2399-3642
  • Schlagwörter: General Agricultural and Biological Sciences ; General Biochemistry, Genetics and Molecular Biology ; Medicine (miscellaneous)
  • Entstehung:
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  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>Vascular leakage, or edema, is a serious complication of acute allergic reactions. Vascular leakage is triggered by the release of histamine and serotonin from granules within tissue-resident mast cells. Here, we show that expression of Neutrophil Serine Protease 4 (NSP4) during the early stages of mast cell development regulates mast cell-mediated vascular leakage. In myeloid precursors, the granulocyte–macrophage progenitors (GMPs), loss of NSP4 results in the decrease of cellular levels of histamine, serotonin and heparin/heparan sulfate. Mast cells that are derived from NSP4-deficient GMPs have abnormal secretory granule morphology and a sustained reduction in histamine and serotonin levels. Consequently, in passive cutaneous anaphylaxis and acute arthritis models, mast cell-mediated vascular leakage in the skin and joints is substantially reduced in NSP4-deficient mice. Our findings reveal that NSP4 is required for the proper storage of vasoactive amines in mast cell granules, which impacts mast cell-dependent vascular leakage in mouse models of immune complex-mediated diseases.</jats:p>
  • Zugangsstatus: Freier Zugang