Macrophage origin and activity is complex in response to acute lung injury. Inducible nitric oxide synthase (iNOS) has a divergent role in the stages following intratracheal bleomycin mediated lung injury (ITB). We hypothesize iNOS is necessary for macrophage activation during the inflammatory and resolution phases that follow ITB. Further, recruited macrophages classically activate during inflammation and resident macrophages alternatively activate during resolution. To test these hypotheses, iNOS was manipulated via scavenge of products, systemic selective iNOS inhibition and chimeric mice in which particular populations were NOS2-/-. C57/BL6 mice were intratracheally instilled with bleomycin and samples collected 8 and 15 days following instillation. This work identified oxidants to promote inflammation during the early stages following ITB. Systemic iNOS inhibition reduced classical activation of recruited macrophages during inflammation and alternative activation of recruited macrophages during resolution. Resident macrophage alternative activation was not dependent on iNOS activity. Chimeric mice demonstrated iNOS of a particular cell population is necessary for macrophage activation. Classical activation of recruited cells is dependent on recruited cell iNOS. Early alternative activation is promoted when recruited macrophages were iNOS incompetent. A pulmonary source of iNOS plays a role in alternative activation during resolution. This work has demonstrated iNOS is important to classical and alternative activation of macrophages. The cell population expressing iNOS determines the effect on activation. The complexity of macrophage populations and effect of iNOS activity on macrophage activation furthers our understanding of the response to ITB and adapted therapeutic approaches have potential for clinical improvement.
Subject (authority = RUETD)
Topic
Toxicology
Subject (authority = ETD-LCSH)
Topic
Lungs--Wounds and injuries
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_7590
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (xii, 137 p. : ill.)
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Thea Noreen Golden
RelatedItem (type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
Rutgers University. Graduate School - New Brunswick
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.