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Title
Characterization of the protein microenviroment of the folate receptor beta / submitted by Mag. rer. nat. Christian Machacek
Additional Titles
Charakterisierung der Proteinmikroumgebung von Folatrezeptor beta
AuthorMachacek, Christian Norbert
Thesis advisorStockinger, Hannes
PublishedWien, 03/2017
Descriptionxii, 87 Seiten : Diagramme
Institutional NoteMedizinische Universität, Dissertation, 2017
Annotation
Zusammenfassung in deutscher Sprache
Abweichender Titel laut Übersetzung der Verfasserin/des Verfassers
Date of SubmissionMarch 2017
LanguageEnglish
Bibl. ReferenceOeBB
Document typeDissertation (PhD)
Keywords (DE)Makrophagen / Adhäsion / Folatrezeptor
Keywords (EN)macrophage / adhesion / folate receptor / ARDS / BAL / cytospin / FACS / flow cytometry / acute respiratory distress / ALI
URNurn:nbn:at:at-ubmuw:1-9783 Persistent Identifier (URN)
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 The work is publicly available
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Characterization of the protein microenviroment of the folate receptor beta [10.67 mb]
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Abstract (German)

Marker für diese funktionell unterschiedlichen Makrophagen mithilfe eines bispezifischen Antikörpers zu verbessern. In weiterer Folge, haben wir die Informationen über die Proteinumgebung zur funktionellen Charakterisierung von FR genutzt. Als Resultat dieser Strategie haben wir eine funktionelle Interaktion zwischen FR und dem Integrin Heterodimer CD11b/CD18 entdeckt, welche in einer Konformationsänderung von CD11b/CD18 resultiert. Diese Interaktion verringert die Fähigkeit von primären menschlichen Makrophagen sowie von FR-transduzierten THP-1 Zellen auf Kollagen zu adhärieren und durch kollagenreiche Gewebe zu migrieren. Daher haben wir FR als neuen Regulator der Migration von Makrophagen identifiziert. hinsichtlich der daran beteiligten Zellen genau zu beschreiben und erlaubt damit Rückschlüsse, auf den zeitlichen und qualitativen Ablauf der Abwehrreaktion im Rahmen eines ARDS.

Abstract (English)

Macrophages are a heterogeneous population of immune cells that fulfill essential functions in the defense against pathogens as well as the maintenance of tissue integrity and remodeling of tissues. However, errant macrophages pose a serious threat to the organism as a whole as they can either fuel inflammation in chronic inflammatory disorders or block effective immune surveillance in the tumor microenvironment. This heterogeneity complicates effective therapy, as indiscriminative targeting of macrophages leads to severe side effects in tissue homeostasis or fighting infections. Folate receptor beta (FR), a GPI anchored protein that is selectively expressed in activated macrophages, was proposed as a promising marker of harmful macrophage populations. To further investigate the applicability of FR, we characterized the protein microenvironment of FR to identify interacting proteins for use in bispecfic targeting of specific macrophage subpopulations and utilized this proteomic information to decipher the function of FR. As a result of this strategy, we detected FR-proximal proteins, which can be utilized to discriminate functionally diverse macrophage populations. More importantly, we detected a functional interaction between FR and the integrin heterodimer CD11b/CD18. This interaction changes the conformation of CD11b/CD18 and regulates adhesion to collagen in FR-transduced THP-1 cells and human primary macrophages. Further, we found that FR-expressing cells display a reduced ability to migrate through collagen-rich matrixes and thereby identified FR as a novel regulator of macrophage homing.

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