Degree Name

PhD (Doctor of Philosophy)


Biomedical Sciences

Date of Award


Committee Chair or Co-Chairs

Valentin Yakubenko

Committee Members

Tammy Ozment, Robert Schoborg, Antonio Rusinol, Chuanfu Li


Sepsis is a life-threatening condition characterized by overwhelming inflammation, resulting in organ system damage, leading to a high mortality rate. Care in the clinical setting is supportive, and there are no approved sepsis-specific treatments. In septic mice, activation of the cholinergic anti-inflammatory pathway decreases cytokine secretion by leukocytes and improves survival. The cholinergic anti-inflammatory pathway is a reflex of the parasympathetic nervous system, converging on the α7 nicotinic acetylcholine (α7nAChR) at the surface of macrophages. Signaling through the receptor blocks NF-kB activation, thus cytokine secretion. Receptor activation has other effects on macrophages, including modulating their migration to target tissues during inflammation. The goal of this study was to describe the contribution of α7nAChR to macrophage migration during sepsis, using both activation with agonist PNU-282987 and α7nAChR-/- mice. We showed that α7nAChR-deficiency impedes migration to inflamed tissues, and that α7nAChR activation promotes macrophage accumulation in tissues, an effect mediated through altered expression of integrin aMb2.

Document Type

Dissertation - unrestricted


Copyright by Kasey Keever.