Multistep IgE Mast Cell Desensitization Is a Dose- and Time-Dependent Process Partially Regulated by SHIP-1

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorADNAN, Ather
dc.contributor.authorACHARYA, Shree
dc.contributor.authorALENAZY, Leila A.
dc.contributor.authorVECILLAS, Leticia de las
dc.contributor.authorBIANCHI, Pedro Giavina
dc.contributor.authorPICARD, Matthieu
dc.contributor.authorCALBACHE-GIL, Lucia
dc.contributor.authorROMERO-PINEDO, Salvador
dc.contributor.authorABADIA-MOLINA, Ana Clara
dc.contributor.authorKERR, William
dc.contributor.authorPEDICONE, Chiara
dc.contributor.authorNAGAI, Jun
dc.contributor.authorHOLLERS, Eleanor
dc.contributor.authorDWYER, Daniel
dc.contributor.authorCASTELLS, Mariana
dc.date.accessioned2023-08-16T17:45:40Z
dc.date.available2023-08-16T17:45:40Z
dc.date.issued2023
dc.description.abstractMultistep mast cell desensitization blocks the release of mediators following IgE crosslinking with increasing doses of Ag. Although its in vivo application has led to the safe reintroduction of drugs and foods in IgE-sensitized patients at risk for anaphylaxis, the mechanisms of the inhibitory process have remained elusive. We sought to investigate the kinetics, membrane, and cytoskeletal changes and to identify molecular targets. IgE-sensitized wild-type murine (WT) and FcERIa humanized (h) bone marrow mast cells were activated and desensitized with DNP, nitrophenyl, dust mites, and peanut Ags. The movements of membrane receptors, FcERI/ IgE/Ag, actin, and tubulin and the phosphorylation of Syk, Lyn, P38-MAPK, and SHIP-1 were assessed. Silencing SHIP-1 protein was used to dissect the SHIP-1 role. Multistep IgE desensitization of WT and transgenic human bone marrow mast cells blocked the release of 13-hexosaminidase in an Ag-specific fashion and prevented actin and tubulin movements. Desensitization was regulated by the initial Ag dose, number of doses, and time between doses. FcERI, IgE, Ags, and surface receptors were not internalized during desensitization. Phosphorylation of Syk, Lyn, p38 MAPK, and SHIP-1 increased in a dose -response manner during activation; in contrast, only SHIP-1 phosphorylation increased in early desensitization. SHIP-1 phosphatase function had no impact on desensitization, but silencing SHIP-1 increased 13-hexoxaminidase release, preventing desensitization. Multistep IgE mast cell desensitization is a dose-and time-regulated process that blocks 13-hexosaminidase, impacting membrane and cytoskeletal movements. Signal transduction is uncoupled, favoring early phosphorylation of SHIP-1. Silencing SHIP-1 impairs desensitization without implicating its phosphatase function.eng
dc.description.indexMEDLINE
dc.description.indexPubMed
dc.description.indexWoS
dc.description.indexScopus
dc.description.sponsorshipInstituto de Investigacion Marques de Valdecilla-IDIVAL (Santander, Spain)
dc.description.sponsorshipPlan Estatal de Investigacion Cientifica y Tecnica y de Innovacion 2013-2016
dc.description.sponsorshipISCIII-Subdireccion General de Evaluacion y Fomento de la Investigacion, Ministerio de Economia y Competitividad, Spain [PI10/01096, PP2014.01]
dc.description.sponsorshipPlan Propio de la Universidad de Granada, Spain 2014 [PI16/01642]
dc.identifier.citationJOURNAL OF IMMUNOLOGY, v.210, n.6, 2023
dc.identifier.doi10.4049/jimmunol.2100485
dc.identifier.eissn1550-6606
dc.identifier.issn0022-1767
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/54592
dc.language.isoeng
dc.publisherAMER ASSOC IMMUNOLOGISTSeng
dc.relation.ispartofJournal of Immunology
dc.rightsrestrictedAccesseng
dc.rights.holderCopyright AMER ASSOC IMMUNOLOGISTSeng
dc.subject.wosImmunologyeng
dc.titleMultistep IgE Mast Cell Desensitization Is a Dose- and Time-Dependent Process Partially Regulated by SHIP-1eng
dc.typearticleeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.affiliation.countryÁrabia Saudita
hcfmusp.affiliation.countryCanadá
hcfmusp.affiliation.countryEspanha
hcfmusp.affiliation.countryEstados Unidos
hcfmusp.affiliation.countryisous
hcfmusp.affiliation.countryisosa
hcfmusp.affiliation.countryisoes
hcfmusp.affiliation.countryisoca
hcfmusp.author.externalADNAN, Ather:Brigham & Womens Hosp, Harvard Med Sch, Dept Med, Div Allergy & Immunol, Boston, MA USA; Texas A&M Hlth Sci Ctr, Coll Med, Houston, TX USA
hcfmusp.author.externalACHARYA, Shree:Brigham & Womens Hosp, Harvard Med Sch, Dept Med, Div Allergy & Immunol, Boston, MA USA
hcfmusp.author.externalALENAZY, Leila A.:Brigham & Womens Hosp, Harvard Med Sch, Dept Med, Div Allergy & Immunol, Boston, MA USA; King Saud Univ, Coll Med, Dept Med, Div Allergy & Clin Immunol, Riyadh, Saudi Arabia
hcfmusp.author.externalVECILLAS, Leticia de las:Brigham & Womens Hosp, Harvard Med Sch, Dept Med, Div Allergy & Immunol, Boston, MA USA; Marques Valdecilla Univ Hosp, Dept Allergy, Inst Invest Marques Valdecilla, Santander, Spain
hcfmusp.author.externalPICARD, Matthieu:Univ Montreal, Hop Maisonneuve Rosemont, Dept Med, Div Allergy & Clin Immunol, Montreal, PQ, Canada
hcfmusp.author.externalCALBACHE-GIL, Lucia:Univ Granada, Unidad Inmunol, IBIMER, CIBM, Granada, Spain; Univ Granada, Fac Med, Dept Bioquim & Biol Moleculare Inmunol 3, Granada, Spain
hcfmusp.author.externalROMERO-PINEDO, Salvador:Univ Granada, Unidad Inmunol, IBIMER, CIBM, Granada, Spain; Univ Granada, Fac Med, Dept Bioquim & Biol Moleculare Inmunol 3, Granada, Spain
hcfmusp.author.externalABADIA-MOLINA, Ana Clara:Univ Granada, Unidad Inmunol, IBIMER, CIBM, Granada, Spain; Univ Granada, Fac Med, Dept Bioquim & Biol Moleculare Inmunol 3, Granada, Spain
hcfmusp.author.externalKERR, William:SUNY Upstate Med Univ, Dept Microbiol & Immunol, Syracuse, NY USA
hcfmusp.author.externalPEDICONE, Chiara:SUNY Upstate Med Univ, Dept Microbiol & Immunol, Syracuse, NY USA
hcfmusp.author.externalNAGAI, Jun:Brigham & Womens Hosp, Harvard Med Sch, Dept Med, Div Allergy & Immunol, Boston, MA USA
hcfmusp.author.externalHOLLERS, Eleanor:Brigham & Womens Hosp, Harvard Med Sch, Dept Med, Div Allergy & Immunol, Boston, MA USA
hcfmusp.author.externalDWYER, Daniel:Brigham & Womens Hosp, Harvard Med Sch, Dept Med, Div Allergy & Immunol, Boston, MA USA
hcfmusp.author.externalCASTELLS, Mariana:Brigham & Womens Hosp, Harvard Med Sch, Dept Med, Div Allergy & Immunol, Boston, MA USA; Brigham & Womens Hosp, 60 Fenwood Rd,Room 5002N, Boston, MA 02115 USA
hcfmusp.citation.scopus6
hcfmusp.contributor.author-fmusphcPEDRO FRANCISCO GIAVINA-BIANCHI JUNIOR
hcfmusp.description.issue6
hcfmusp.description.volume210
hcfmusp.origemWOS
hcfmusp.origem.pubmed36881903
hcfmusp.origem.scopus2-s2.0-85149549531
hcfmusp.origem.wosWOS:001013083600002
hcfmusp.publisher.cityBETHESDAeng
hcfmusp.publisher.countryUSAeng
hcfmusp.scopus.lastupdate2024-05-10
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relation.isAuthorOfPublication.latestForDiscovery5aeba5b1-a416-4d64-931a-1d3750f77ad4
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