Publikationsserver der Universitätsbibliothek Marburg

Titel:Untersuchungen der Expression von Neurotrophinen und Neurotrophin-Rezeptoren auf murinen B-Zellen im Knochenmark und in der Milz von C57BL/6
Autor:Emmel, Jörg
Weitere Beteiligte: Renz, Harald (Prof. Dr. med.)
Veröffentlicht:2010
URI:https://archiv.ub.uni-marburg.de/diss/z2010/0239
DOI: https://doi.org/10.17192/z2010.0239
URN: urn:nbn:de:hebis:04-z2010-02392
DDC: Medizin
Titel (trans.):Analysis of neurotrophin and neurotrophin- receptor expression of murine b-cells in bone marrow and spleen of C57BL/6 wildtype mice
Publikationsdatum:2010-04-27
Lizenz:https://rightsstatements.org/vocab/InC-NC/1.0/

Dokument

Schlagwörter:
Brain-derived neurotrophic factor, NT-3, Real time quantitative PCR, trkA, NT-3, Nervenwachstumsfaktor, trkC, Neurotrophin-Rezeptor, trkC, Milz, trkA, FACS, trkBgp95, NT-4/5, FACS, trkBgp145, Knochenmark, NT-4/5, Neurotrophine, Polymerase-Kettenreaktion, neurotrophin-receptor, neurotrophine, B-Zelle, trkBgp145, trkBgp95

Zusammenfassung:
Neurotrophine sind lösliche, nicht kovalent gebundene Homodimerpeptide, die initial im Zentralnervensystem von Vertebraten detektiert worden sind. Sie vermitteln dort in erster Linie anti-apoptotische Effekte wie Proliferation, Differenzierung, Überleben der Zelle und Schutz vor zytotoxischen Zellschaden; daneben sind auch nicht-topische Effekte wie Induktion von Chemotaxis zur regelrechten Axonsprossung bekannt. Hauptvertreter sind NGF, BDNF, NT-3 und NT-4/5. Dabei werden Neurotrophine nicht nur die Zielzelle umgebenen Zellen sezerniert, sondern auch durch die Zielzelle selbst im Sinne autokriner Mechanismen. Die Effekte der Neurotrophine werden durch zwei Familien von Neurotrophine-Rezeptoren vermittelt: die Tyrosinkinase-Glykoprotein-Rezeptoren binden nur bestimmte Neurotrophine mit hoher Affinität und vermitteln anti-apoptotische Effekte. Sie werden in 3 Klassen unterschieden: trkA, trkB und trkC. Dabei werden durch die Zielzelle durch alternatives Splicing verschiedene Isoformen dieser Rezeptoren exprimiert, darunter auch solche die keine katalytische Tyrosinkinase-Domäne beinhalten. Ein weiterer Rezeptor ist der Pan-Neurotrophin-p75-Rezeptor, der alle Neurotrophine mit gleicher Affinität bindet. Er vermittelt bivalente Funktionen: bei Anwesenheit von trk-Rezeptoren antia-apoptotische Effekte, bei Abwesenheit von trk-Rezeptoren pro-apoptototische Effekte. In den letzten 20 Jahren wurde etraneuronal insbesondere auf Immunzellen Neurotrophin-Synthese und Neurotrophin-Rezeptor-Expression detektiert. Hinsichtlich der B-Zellen zeigen sich jedoch divergente Angaben. Einige Autoren belegen, daß die B-Zelle alle Neurotrophine und deren Rezeptoren exprimiert, andere Autoren belegen lediglich eine Expression von trkA und p75. Dabei sind in diesen Arbeiten einige Limitationen offensichtlich: Verwendung von malignen B-Zellen bzw- EBV-transformierten B-Zellen und Verwendung immunhistochemischer Nachweisverfahren. In dieser Arbeit wurde mittels molekularbiologischer Methodik eine umfassende Charakterisierung der unreifen B-Zellen des Knochenmarks und reifer B-Zellen (exemplarisch in der Milz) in einer Wildtyp-Maus verwirklicht. Dabei zeigt sich, daß reife wie unreife B-Zellen alle bekannten Neurotrophine und deren Rezeptoren exprimiert. Eine Ausnahme besteht jedoch hinsichtlich des trkB-Rezeptors; dieser wird nur in einer Isoform exprimiert, die keine katalytische Tyrosinkinase-Domäne besitzt (trkBgp95). In der quantitativen real-time-PCR zeigt sich, daß BDNF das dominante Neurotrophin der unreifen B-Zelle im Knochenmark und NT-3 und NGF das dominante Neurotrophin der reifen B-Zelle ist. Hinsichtlich der Neurotrophin-Rezeptoren gibt es keine quantitativen Unterschiede, lediglich der Neurotrophin-Rezeptor trkC wird geringradig mehr durch die unreifen B-Zellen des Knochenmarks exprimiert.

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