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Georgia Tech

1. Amos, Amanda Owings. Regulation of Cytokine-Induced Adhesion Molecule Expression and Sickle Erythrocyte Adhesion to Microvascular Endothelial Cells by Intracellular Adenosine 3',5'-Cyclic Monophosphate and Nitric Oxide.

Degree: PhD, Chemical Engineering, 2006, Georgia Tech

Adhesion of sickle erythrocytes to vascular endothelium may initiate or propagate occlusive events in sickle cell anemia, many of which are accompanied by infection and the associated inflammatory response. Inflammatory markers are also present in sickle patients during asymptomatic periods. Inflammatory cytokines upregulate expression of endothelial adhesion molecules that promote adhesion of sickle erythrocytes. The data in this work demonstrate that after 2 hrs of stimulation with the cytokine TNF- and alpha;, E-selectin, but not VCAM-1 is upregulated on human dermal microvascular endothelial cells. After 6 hrs of TNF- and alpha; stimulation, both VCAM-1 and E-selectin expression are upregulated on MECs, and sickle erythrocytes bind to both receptors. Because strategies to control inflammation-associated adhesion in vivo may need to account for both VCAM-1 and E-selectin mediated events, control of intracellular signaling pathways leading to receptor expression is an attractive strategy for inhibiting adhesion. Cyclic AMP and nitric oxide are two intracellular signaling molecules important to cytokine-induced receptor expression. The data in this work demonstrate that TNF- and alpha; induced VCAM-1 and E-selectin expression on endothelial cells and sickle erythrocyte adhesion are abated by increasing endothelial cyclic AMP concentrations using Forskolin, IBMX, or Bt2cAMP. Conversely, when sickle erythrocytes, rather than endothelial cells, are treated with reagents that increase intracellular cAMP, adhesion to unstimulated endothelial cells is increased in some patients. Treatment of endothelial cells with reagents such as SNP and DETA-NO that increase nitric oxide significantly inhibits VCAM-1, but not E-selectin expression, induced by TNF- and alpha; stimulation and significantly inhibits sickle erythrocyte adhesion. Treatment of sickle erythrocytes directly with these reagents may also inhibit adhesion. Together these data suggest that cAMP- and nitric oxide-dependent signaling are useful therapeutic targets to inhibit cytokine-induced sickle erythrocyte adhesion to endothelium. Advisors/Committee Members: Dr. Timothy M. Wick (Committee Chair), Dr. James R. Eckman (Committee Member), Dr. Larry V. McIntire (Committee Member), Dr. Peter A. Lane (Committee Member), Dr. Ronald W. Rousseau (Committee Member).

Subjects/Keywords: Cyclic AMP; Adhesion; Sickle cell anemia; Nitric oxide; Sickle cell anemia; Vascular endothelium; Cell adhesion molecules; Cytokines; Erythrocytes; Inflammation

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Amos, A. O. (2006). Regulation of Cytokine-Induced Adhesion Molecule Expression and Sickle Erythrocyte Adhesion to Microvascular Endothelial Cells by Intracellular Adenosine 3',5'-Cyclic Monophosphate and Nitric Oxide. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/14621

Chicago Manual of Style (16th Edition):

Amos, Amanda Owings. “Regulation of Cytokine-Induced Adhesion Molecule Expression and Sickle Erythrocyte Adhesion to Microvascular Endothelial Cells by Intracellular Adenosine 3',5'-Cyclic Monophosphate and Nitric Oxide.” 2006. Doctoral Dissertation, Georgia Tech. Accessed March 03, 2021. http://hdl.handle.net/1853/14621.

MLA Handbook (7th Edition):

Amos, Amanda Owings. “Regulation of Cytokine-Induced Adhesion Molecule Expression and Sickle Erythrocyte Adhesion to Microvascular Endothelial Cells by Intracellular Adenosine 3',5'-Cyclic Monophosphate and Nitric Oxide.” 2006. Web. 03 Mar 2021.

Vancouver:

Amos AO. Regulation of Cytokine-Induced Adhesion Molecule Expression and Sickle Erythrocyte Adhesion to Microvascular Endothelial Cells by Intracellular Adenosine 3',5'-Cyclic Monophosphate and Nitric Oxide. [Internet] [Doctoral dissertation]. Georgia Tech; 2006. [cited 2021 Mar 03]. Available from: http://hdl.handle.net/1853/14621.

Council of Science Editors:

Amos AO. Regulation of Cytokine-Induced Adhesion Molecule Expression and Sickle Erythrocyte Adhesion to Microvascular Endothelial Cells by Intracellular Adenosine 3',5'-Cyclic Monophosphate and Nitric Oxide. [Doctoral Dissertation]. Georgia Tech; 2006. Available from: http://hdl.handle.net/1853/14621

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