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

Communications Biology
Andrew P AhYoungMenno van Lookeren Campagne

Abstract

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.

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References

Jul 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·M TsaiS J Galli
Oct 1, 1993·British Journal of Pharmacology·C Zuany-AmorimM Pretolani
Oct 7, 1998·Biochemistry·D L RabensteinJ Peng
Jul 26, 2002·Natural Product Reports·Dallas L Rabenstein
Dec 12, 2002·Trends in Endocrinology and Metabolism : TEM·Robert Day, Sven Ulrik Gorr
Jan 31, 2006·Nature Immunology·Bryce A BinstadtChristophe Benoist
Jun 27, 2006·Nature Reviews. Immunology·Christine T N Pham
May 4, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Odile MalbecMarc Daëron
Nov 21, 2007·Journal of Dermatological Science·Stephen J Galli, Mindy Tsai
Dec 15, 2007·The American Journal of Pathology·Alexander Zarbock, Klaus Ley
Feb 1, 2008·The Journal of Allergy and Clinical Immunology·Maria RingvallGunnar Pejler
Feb 6, 2008·Proceedings of the National Academy of Sciences of the United States of America·Niti Puri, Paul A Roche
May 21, 2009·Analytical Biochemistry·Baoyun XiaRichard D Cummings
Feb 12, 2010·Bioinformatics·Thomas D Wu, Serban Nacu
May 26, 2010·Nature Reviews. Immunology·Soman N Abraham, Ashley L St John
Jun 22, 2010·Nature Biotechnology·Tracy TangFrederic J de Sauvage
Sep 13, 2011·Blood·Christian A KunderSoman N Abraham
Apr 5, 2012·Proceedings of the National Academy of Sciences of the United States of America·Natascha C PereraDieter E Jenne
May 9, 2012·Nature Medicine·Stephen J Galli, Mindy Tsai
Nov 1, 2012·Proceedings of the National Academy of Sciences of the United States of America·Christian D SadikAndrew D Luster
Aug 2, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Natascha C PereraDieter E Jenne
Sep 5, 2013·European Journal of Immunology·Shunsuke NakazawaSatoshi Tanaka
Nov 12, 2013·Immunity·Thomas MarichalStephen J Galli
Feb 4, 2014·Genome Biology·Charity W LawGordon K Smyth
Jun 7, 2014·Nature Reviews. Immunology·Sara Wernersson, Gunnar Pejler
Dec 3, 2014·Current Opinion in Microbiology·Daphne A C StapelsSuzan H M Rooijakkers
Jan 22, 2015·Nucleic Acids Research·Matthew E RitchieGordon K Smyth
Mar 10, 2015·Stem Cells and Development·Joakim S DahlinJenny Hallgren
May 27, 2016·Seminars in Immunopathology·Kaori MukaiStephen J Galli
Jun 18, 2016·Frontiers in Immunology·Anne D ChristensenJohn A Hamilton
Aug 26, 2016·Immunological Reviews·Jack B Cowland, Niels Borregaard
Jul 4, 2017·Journal of the American Chemical Society·Paulina KasperkiewiczMarcin Drag
Jul 9, 2017·Immunology and Allergy Clinics of North America·Parwinder Gill, Stephen D Betschel

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Citations

May 1, 2021·International Journal of Molecular Sciences·Martin VossAnne Dudeck

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Methods Mentioned

BETA
flow cytometry
scanning electron microscopy
lavage
enzyme-linked immunosorbent assay
PCA
FACS
PCR
ELISA
PMA
fluorescence imaging

Software Mentioned

HTSeqGenie Bioconductor
R
SmartSEM
GraphPad
COR
FlowJo
limma
Pearl Cam
Li
BD FACS Diva

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