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Regulation of macrophage phenotype by S-nitrosylation during pulmonary inflammatory responses

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TitleInfo
Title
Regulation of macrophage phenotype by S-nitrosylation during pulmonary inflammatory responses
Name (type = personal)
NamePart (type = family)
Taylor
NamePart (type = given)
Sheryse
NamePart (type = date)
1990-
DisplayForm
Sheryse Taylor
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
GOW
NamePart (type = given)
ANDREW
DisplayForm
ANDREW GOW
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
School of Graduate Studies
Role
RoleTerm (authority = RULIB)
school
TypeOfResource
Text
Genre (authority = marcgt)
theses
OriginInfo
DateCreated (encoding = w3cdtf); (qualifier = exact)
2019
DateOther (encoding = w3cdtf); (qualifier = exact); (type = degree)
2019-05
CopyrightDate (encoding = w3cdtf); (qualifier = exact)
2019
Language
LanguageTerm (authority = ISO 639-3:2007); (type = text)
English
Abstract (type = abstract)
The pulmonary microenvironment is truly unique as it is continuously exposed to insult through inhalation of pollution and microbes, tasking the pulmonary immune system with active maintenance of homeostasis. In the lung the resident immune cell is the alveolar macrophage. These cells, along with bone marrow derived infiltrating macrophages are capable of developing responses that can be characterized along a pro-inflammatory or pro-repair spectrum, which is dictated in part by the microenvironment. For example, resident alveolar macrophages are largely anti-inflammatory as the lung contains a number of immunosuppressive mechanisms to prevent activation. These macrophages surveil the lung and when necessary, mount an immune response to preserve lung function. Key to this inflammatory response in macrophages is inducible Nitric Oxide Synthase (iNOS) and iNOS derived nitric oxide (NO). NO can react with a large number of biological targets, the majority of which fall under three major categories: reactive oxygen and nitrogen species (RONS), metals and thiols. NO’s thiol based reactions serve as a signaling mechanism, forming S-nitrosothiols (SNOs) on proteins and small peptides. Formation of SNOs modifies the activity and function of a variety of proteins including enzymes and transcription factors, many of which have been implicated in macrophage activation and inflammatory signaling. Loss of NO has been found to alter the immune response in a model, and time dependent manner. Whether through genetic ablation or inhibition, loss of iNOS derived NO has been found to both reduce acute lung injury (ALI) in models of ozone, bleomycin, and LPS and worsen hyperoxia induced ALI, and bleomycin induced fibrosis. It is unclear which of NO’s bioactivity contributes to the previously observed effects, as well as the extent of NO’s thiol based signaling on regulation of macrophage activation. Using models of acute lung injury, fibrosis and adenocarcinoma the present studies confirm previous findings of model induced changes in macrophage activation, and then determine how increased SNO formation affected macrophage phenotype in these models. Using multiple methods of immunophenotyping, we observed that SNO formation limited pro-inflammatory macrophage activation in models of pulmonary inflammation. Additionally, consistent with microenvironment/macrophage crosstalk, these changes altered immune signaling in the lung microenvironment. In general, these changes in macrophage phenotype and immune signaling led to alterations in biomarkers of disease progression. Also observed were the effects of SNO signaling in multiple macrophage subsets, primarily observing differences in resident lung populations as opposed to those recruited to the lung, and alveolar space during inflammatory signaling. Our findings suggest that NO’s thiol based signaling present an opportunity to regulate inflammatory signaling and macrophage activation, as well as demonstrate the contribution of macrophage phenotype to the lung microenvironment.
Subject (authority = RUETD)
Topic
Toxicology
Subject (authority = LCSH)
Topic
Macrophages -- Genetic aspects
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_9827
PhysicalDescription
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InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (xiii, 115 pages) : illustrations
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
RelatedItem (type = host)
TitleInfo
Title
School of Graduate Studies Electronic Theses and Dissertations
Identifier (type = local)
rucore10001600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier (type = doi)
doi:10.7282/t3-5jg2-rt96
Genre (authority = ExL-Esploro)
ETD doctoral
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Rights

RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Taylor
GivenName
Sheryse
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2019-04-12 07:28:55
AssociatedEntity
Name
Sheryse Taylor
Role
Copyright holder
Affiliation
Rutgers University. School of Graduate Studies
AssociatedObject
Type
License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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windows xp
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2019-04-23T15:00:37
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2019-04-23T11:01:04
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