Advisory Committee Chair
Rakesh P Patel
Advisory Committee Members
Shannon Bailey
Victor Darley-Usmar
Jeannette Doeller
Sadis Matalon
Document Type
Dissertation
Date of Award
2010
Degree Name by School
Doctor of Philosophy (PhD) Heersink School of Medicine
Abstract
The recent discovery that red blood cells might mediate hypoxic blood flow together with accumulating evidence that suggests a role for the modulation of vascular inflammation has reshaped the way we think about the function of these cells. In this thesis we investigate the mechanisms that regulate these newly appreciated functions and focus on i) the ability of red cells to couple oxygen sensing with nitrite reduction and nitric oxide formation and ii) the role of the beta93cys, a conserved residue amongst mammalian hemoglobins and whose function remains unclear. Data will be presented that demonstrate that nitrite reduction to nitric oxide by red blood cells is regulated by an oxygen-sensitive mechanism that controls nitrite transport through the cell membrane. Additionally, evidence will be provided showing that the nitrite reductase activity of heme proteins can be harnessed for the development of clinically viable hemoglobin based blood substitutes. More specifically we show that coadministration of sodium nitrite prevents the hypertensive response commonly observed after transfusion with a hemoglobin-based blood substitute. Finally, data will be presented that suggest that the beta93cys residue modulates acute vascular and pulmonary inflammation via reactions with reactive oxygen and chlorine species which in turn may protect against vascular and end organ injury in acute inflammation
Recommended Citation
Vitturi, Dario A., "Red Blood Cell And Hemoglobin Dependent Modulation Of Reactive Species Metabolism: Implications For Vascular Homeostasis" (2010). All ETDs from UAB. 3226.
https://digitalcommons.library.uab.edu/etd-collection/3226