Regulation of macrophage growth and function by IFN-gamma

dc.contributor.authorGoldberg, Michael Raoul
dc.date.accessioned2018-07-12T18:32:09Z
dc.date.available2018-07-12T18:32:09Z
dc.date.issued1989
dc.description.abstractMacrophages play a major role in the immune response against invading pathogens and are uniquely regulated by interferon gamma {dollar}\{lcub}{dollar}IFN {dollar}\gamma\{rcub}{dollar}. A somatic cell genetic approach was used to analyze the pleiotropic effects of IFN {dollar}\gamma{dollar} on macrophages, e.g. antiviral, anti-proliferative effects, and activation of the respiratory burst, and to determine whether the effects are mediated by the same signals and/or the same effector mechanisms. Somatic variants in a murine macrophage-like cell line were selected that had defects in specific IFN {dollar}\gamma{dollar} regulated functions. The anti-proliferative and antiviral activities of IFN {dollar}\gamma{dollar} could be formally dissociated. Biochemical analysis of variants revealed that both IFN {dollar}\alpha{dollar} and IFN {dollar}\gamma{dollar} utilize the dsRNA dependent eukaryotic initiation factor-2 {dollar}\{lcub}{dollar}eIF-2{dollar}\{rcub}{dollar} kinase system to effect the antiviral state against infection with vesicular stomatitis virus and encephalomyocarditis virus, although they can each regulate the eIF-2 kinase system via different pathways.;Unexpectedly, a genetic association existed between the respiratory burst and the anti-proliferative effects of IFN {dollar}\gamma{dollar}. Variants selected for their inability to produce O{dollar}\sb{lcub}2{rcub}\sp{lcub}-{rcub}{dollar} in response to phorbol esters were resistant to the anti-proliferative effects of IFN {dollar}\gamma{dollar}. It thus appears, a protein kinase C mediated pathway is implicated in the anti-proliferative effects of IFN {dollar}\gamma{dollar} in the mouse macrophages. Finally, Northern analysis of a variant defective in the oxidative burst revealed the absence of the transcript for the chronic granulomatous disease {dollar}\{lcub}{dollar}CGD{dollar}\{rcub}{dollar} gene. This variant should be useful to study the structure function relationships and/or the gene regulation of the CGD gene locus.
dc.identifier.citationSource: Dissertation Abstracts International, Volume: 51-04, Section: B, page: 1634.;Advisors: Barry R. Bloom.
dc.identifier.urihttps://ezproxy.yu.edu/login?url=http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqm&rft_dat=xri:pqdiss:9025476
dc.identifier.urihttps://hdl.handle.net/20.500.12202/3317
dc.publisherProQuest Dissertations & Theses
dc.subjectMicrobiology.
dc.subjectImmunology.
dc.titleRegulation of macrophage growth and function by IFN-gamma
dc.typeDissertation

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