{"@context":"http://iiif.io/api/presentation/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/manifest.json","@type":"sc:Manifest","label":"The Regulation of Neutrophil Function by the Vitamin D Binding Protein (DBP).","metadata":[{"label":"dc.description.sponsorship","value":"This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree."},{"label":"dc.format","value":"Monograph"},{"label":"dc.format.medium","value":"Electronic Resource"},{"label":"dc.identifier.uri","value":"http://hdl.handle.net/1951/59679"},{"label":"dc.language.iso","value":"en_US"},{"label":"dc.publisher","value":"The Graduate School, Stony Brook University: Stony Brook, NY."},{"label":"dcterms.abstract","value":"Vitamin D binding protein (DBP), also called Gc globulin, is an abundant plasma protein belonging to the albumin gene family.  DBP is primarily known for its role in the transport of vitamin D metabolites in the blood and extracellular fluids, and as an actin scavenger in the circulation.  DBP also has been shown to be a chemotactic cofactor for the complement activation peptide C5a, and a deglycosylated form (DBP-MAF) has been shown to activate macrophages and osteoclasts in vitro.  The in vivo relevance and the mechanism behind the chemotactic cofactor function of DBP is not known.  In this report, a C5a induced alveolitis model was developed and the neutrophil migration into the lungs of DBP -/- and DBP +/+ mice was determined. There was a significant decrease in the number of neutrophils recruited into the lung at 4, 6, and 24 hours after instillation of C5a in DBP -/- mice as compared to DBP +/+ animals.  Ex vivo analysis of DBP -/- bone marrow neutrophils revealed decreased surface expression CD88 (C5a receptor), CD44 (DBP receptor), CD11b (cell adhesion molecule) and decreased side scatter (less internal granularity). Functional analysis of DBP -/- bone marrow neutrophils revealed an intrinsic defect in migration, polarization and superoxide anion generation suggesting a role for DBP in neutrophil differentiation in vivo. This was confirmed using the promyelocytic cell line HL-60, where higher surface expression of CD88, CD44 and higher side scatter was observed when cells were differentiated in the presence of DBP. Finally, a mechanism by which DBP functions during chemotaxis and differentiation is proposed.  Using a proteomic approach, it was observed that DBP treated neutrophils generate DBP-actin complexes which in turn induce secretion the inflammatory amplifier S100A8/A9. This molecule has been implicated in neutrophil chemotaxis, polarization, superoxide anion generation and differentiation.  In vitro analysis of human neutrophils confirmed that DBP treatment induced the generation of DBP-actin complexes and the formation of intracellular S100A8/A9 complexes.  Furthermore, DBP-actin complexes were found to be potent inducers of S100A8/A9 release from neutrophils."},{"label":"dcterms.available","value":"2013-05-22T17:34:42Z"},{"label":"dcterms.contributor","value":"Marcu, Kenneth B"},{"label":"dcterms.creator","value":"Habiel, David Michael"},{"label":"dcterms.dateAccepted","value":"2015-04-24T14:46:41Z"},{"label":"dcterms.dateSubmitted","value":"2013-05-22T17:34:42Z"},{"label":"dcterms.description","value":"Department of Molecular and Cellular Biology"},{"label":"dcterms.extent","value":"193 pg."},{"label":"dcterms.format","value":"Monograph"},{"label":"dcterms.identifier","value":"http://hdl.handle.net/1951/59679"},{"label":"dcterms.issued","value":"2012-05-01"},{"label":"dcterms.language","value":"en_US"},{"label":"dcterms.provenance","value":"Made available in DSpace on 2013-05-22T17:34:42Z (GMT). No. of bitstreams: 1\nHabiel_grad.sunysb_0771E_10846.pdf: 70349380 bytes, checksum: b41b084c87ad1c2bca134e260c868908 (MD5)\n  Previous issue date:    1"},{"label":"dcterms.publisher","value":"The Graduate School, Stony Brook University: Stony Brook, NY."},{"label":"dcterms.subject","value":"Immunology--Pathology--Cellular biology"},{"label":"dcterms.title","value":"The Regulation of Neutrophil Function by the Vitamin D Binding Protein (DBP)."},{"label":"dcterms.type","value":"Dissertation"},{"label":"dc.type","value":"Dissertation"}],"description":"This manifest was generated dynamically","viewingDirection":"left-to-right","sequences":[{"@type":"sc:Sequence","canvases":[{"@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/canvas/page-1.json","@type":"sc:Canvas","label":"Page 1","height":1650,"width":1275,"images":[{"@type":"oa:Annotation","motivation":"sc:painting","resource":{"@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/23%2F02%2F37%2F23023727419612631583658634808151036744/full/full/0/default.jpg","@type":"dctypes:Image","format":"image/jpeg","height":1650,"width":1275,"service":{"@context":"http://iiif.io/api/image/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/23%2F02%2F37%2F23023727419612631583658634808151036744","profile":"http://iiif.io/api/image/2/level2.json"}},"on":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/canvas/page-1.json"}]}]}]}