Honors Theses

Date of Award

5-2026

Document Type

Undergraduate Thesis

Degree Name

BS

Department

Biomedical Sciences

Faculty Mentor

Sarah Sayner, Ph.D.

Advisor(s)

Terrence J. Ravine, Ph.D. and Phoibe Renema, Ph.D.

Abstract

The pulmonary microvascular endothelium holds a unique niche, acting as a component of the alveolar-capillary membrane and a barrier between the blood and surrounding tissues. During severe lung infection, disruption of the pulmonary microvascular endothelial barrier increases permeability, promoting alveolar fluid accumulation. In the short-term, this can progress to respiratory failure. Currently, there is a growing interest in the long-term effects following recovery from severe lung infections. Primary infection with type three secretion system (TTSS) competent Pseudomonas aeruginosa expressing exoenzyme Y (ExoY) induces endothelial cells to release cytotoxic amyloids. In this study, we sought to examine the impact amyloid precursor protein (APP) and its metabolites had on B2 adrenergic signaling post-infection. Herein, we describe how supernatants generated from a P. aeruginosa primary infection alter baseline and agonist-stimulated cyclic adenosine monophosphate (cAMP) responses in pulmonary microvascular endothelial cells (PMVECs). In the absence of agonist stimulation, cytotoxic supernatants derived from wild-type (WT) or amyloid precursor protein knockout (APP-/-) PMVECs did not alter the cAMP response. Cytotoxic supernatants generated from WT PMVECs infected by P. aeruginosa expressing ExoY attenuate B2 adrenergic agonist and transmembrane adenylyl cyclase agonist elevations in cAMP. Control or infection-derived cytotoxic supernatants from APP-/- PMVECs did not elicit significant attenuation of agonist induced cAMP elevation.

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