Degree Name
MS (Master of Science)
Program
Biology
Date of Award
5-2023
Committee Chair or Co-Chairs
Valentin Yakubenko
Committee Members
Chad Frasier, Patrick Bradshaw
Abstract
2-ω-carboxyethylpyrrole (CEP) is a product of docosahexaenoic acid (DHA) oxidation, which forms covalent adducts with different proteins. CEP-modified proteins can interact with macrophage receptor, integrin αDβ2. This study aims to compare αDβ2 binding to its physiological ligand, fibrinogen, and CEP-modified fibrinogen, which is formed during inflammation. We hypothesize that modification of fibrinogen changes its ligand-binding properties to integrin αDβ2 which can affect macrophage migration and retention. Recombinant αD I-domain and αDβ2-transfected HEK293 cells were used for the experiments. Using biolayer interferometry, we found that the affinity of αD I-domain binding to fibrinogen-CEP was higher than fibrinogen and inhibited by the anti-CEP antibody. In agreement, αDβ2-transfected cells demonstrated stronger adhesion to fibrinogen-CEP and this adhesion was significantly inhibited by polyglutamic acid that mimics CEP-mediated binding. These findings suggest that αDβ2's interaction with DHA-modified extracellular matrix (ECM) proteins significantly increases macrophage adhesion and may serve for macrophage retention during chronic inflammation.
Document Type
Thesis - unrestricted
Recommended Citation
Ilesanmi, Ajibola, "Comparative Characteristics of Integrin αDβ2 Binding to Native Fibrinogen and Fibrinogen Modified by DHA Oxidation During Inflammation" (2023). Electronic Theses and Dissertations. Paper 4225. https://dc.etsu.edu/etd/4225
Copyright
Copyright by the authors.