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The Origin Of Mouse Embryonic Mast Cells And The Function Of Peritoneal Mast Cells

Posted on:2017-04-20Degree:DoctorType:Dissertation
Country:ChinaCandidate:Z Q LiFull Text:PDF
GTID:1364330572453010Subject:Immunology
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Part I E7.5 early erythro-myeloid progenitors differentiate into mouse embronic mast cellsMast cells(MCs)originate from pluripotent hematopoietic stem cells have been proved for many years.And the precursors of mast cells have been identified in the bone marrow of adult mice and rats.However,the origin of embryonic mast cells is still not known.Conjugated avidin binds to mast cell granules specificly.So we used avidin-FITC to analyse embryonic mast cells during diferent developmental stages by flow cytometric analysis.We found that,until E16.5,avidin positive mast cells can be detected in all tissues of embryos.And we proved that T1/ST2 combined with c-Kit can be a good marker to identify embryonic mast cells.We also proved that embryonic day(E)12.5 fetal liver cells differentiate into skin and peritonium mast cells.Early EMPs develop in the yolk yac at E7.5,mignate and colonize the nascent fetal liver before E10.5,and give rise to fetal Mast cell-committed progenitor(MCp).Additionally,c-Kit W-sh/W-sh mutation does not intefere the embryonic mast cells differentiation.The differentiation of mast cells in embryos and adult mice are indenpent of Rag2 gene.Mouse embronic mast cells continue to mature after birth,expressing Fc ε RI and Scal.Embronic mast cells in the Skin and peritonium can self-renew,which is maintained indepentently of adult hematopoiesis.Part II Cross-talk between macrophages and mast cells in CXCL1 synthesisNeutrophil recruitment is an important early step in controlling tissue infections or injury.And neutrophil chemoattractants CXCL1/CXCL2(CXC chemokine ligands 1/2)play an import role during this influs.Here,we report that peritoneal Mast cells synthesize chemocine CXCL1 in the first time of intraperitoneal Listeria monocytogenes(LM)and lipopolysaccharide(LPS)stimulation.Resident Macrophages(M)are required for the synthesis of CXCL1 by peritoneal Mast cells.Reduced CXCL1 synthesis and granule release by peritoneal mast cells in mice with M Φ depletion.MΦ and peritoneal mast cells communicate in a cell-cell contact dependent manner.Thioglycollate-elicited mouse peritoneal macrophages and BMDC also can help peritoneal mast cells to synthesize CXCL1.This role of MΦ was inhibited by dexamethasone,Actinomycin D and Extracellular signal-regulated kinaseinhibitors.Additionally,only matured mast cells can synthesize CXCL1.Therefore,we demonstrate that mast cells and infected macrophages communicate directly during an innate immune response to infection.
Keywords/Search Tags:precursors of mast cells, fetal liver, T1/ST2, c-Kit, embryonic mast cll, CXCL1, BMMC, M Φ, LM, LPS, peritoneal MCs, neutrophil
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