Home > General > Entwicklung eines Schwingquarz-basierten Assays zur Detektion der PfEMP1-vermittelten Zytoadhasion von Plasmodium falciparum
Entwicklung eines Schwingquarz-basierten Assays zur Detektion der PfEMP1-vermittelten Zytoadhasion von Plasmodium falciparum

Entwicklung eines Schwingquarz-basierten Assays zur Detektion der PfEMP1-vermittelten Zytoadhasion von Plasmodium falciparum

          
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About the Book

Malaria ist heutzutage nach wie vor die haufigste aller Tropenkrankheiten, die besonders im Fall der Malaria tropica schwerwiegende Krankheitserscheinungen auslosen kann. Bei dieser Form fuhrt die parasitare Infektion unter anderem zu Schadigungen des Gehirns, Anamien und im Falle der plazentalen Malaria zu Fehlgeburten. Verantwortlich fur die Ausbildung derart ernster Symptome ist das ausschließlich bei Plasmodium falciparum auftretende Phanomen der Sequestrierung. Dabei adharieren spate Blutstadien uber verschiedene parasitare Proteine an das Endothel postkapillarer Venolen und konnen im peripheren Blut nicht mehr nachgewiesen werden. Der dabei wichtigste Ligand ist das parasitare Protein Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1). Ziel der vorliegenden Arbeit war es, einen auf der Schwingquarzsensorik basierenden Adhasionsassay zu entwickeln, um neue Einsichten in den Vorgang der Adhasion infizierter Zellen bzw. einzelner PfEMP1-Domanen an die Rezeptoren CD36, Chondroitin-Sulfat A (CSA) und ICAM-1 zu gewinnen. Um dies zu realisieren, wurden verschiedene Schichtsysteme zur Immobilisierung funktionsfahiger Rezeptoren auf den Sensoren entwickelt. Dazu wurden hinsichtlich der Rezeptoren CD36 und ICAM-1 Membranen verschiedener Zelllinien eingesetzt, die diese Rezeptoren trugen. Mit diesen Schichten war es sowohl moglich die spezifische Adhasion infizierter Zellen an die CD36-tragenden Membranen, als auch die spezifische Bindung einzelner PfEMP1-Domanen an CD36 bzw. ICAM-1 nachzuweisen. Hinsichtlich der Domanen konnten dabei bestehende Kenntnisse bestatigt und neue Kenntnisse gewonnen werden, da neue ICAM-1-bindende Domanen identifiziert werden konnten. Zudem waren unterschiedliche Affinitaten bzw. Bindungsstarken einzelner Domanen fur den Rezeptor ICAM-1 festzustellen, was bisher mit konventionellen Methoden nicht moglich ist. Im Hinblick auf die Untersuchung der Adhasion infizierter Zellen an CSA wurde ein von den in der Malariaforschung gangigen Immobilisierungsmethoden abweichendes CSABeschichtungsmodell entwickelt, mit dem eindeutig spezifische Bindungsereignisse nachgewiesen werden konnten. Des Weiteren war zu verzeichnen, dass die zwischen den infizierten Zellen und den Rezeptoren CD36 und CSA aufgebauten Bindungen unterschiedlich stark ausgepragt waren. Die Technologie der Schwingquarz-Biosensorik besitzt konventionellen Methoden gegenuber somit ein enormes Potential fur die Malaria-Forschung. Die in der vorliegenden Arbeit gewonnenen Ergebnisse stellen dabei die Basis fur weitere Untersuchungen hinsichtlich der Grundlagenforschung auf dem Gebiet der Sequestrierung, der Diagnostik und der Medikamentenentwicklung dar.


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Product Details
  • ISBN-13: 9783869557212
  • Binding: Paperback
  • Language: German
  • Width: 233 mm
  • ISBN-10: 3869557214
  • Height: 210 mm
  • Weight: 9 gr

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Entwicklung eines Schwingquarz-basierten Assays zur Detektion der PfEMP1-vermittelten Zytoadhasion von Plasmodium falciparum
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