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Date of Award

Spring 5-15-2015

Author's School

College of Arts & Sciences

Author's Department/Program

Biology

Degree Name

Bachelor of Science

Abstract

Advances in the management of acute lung injury and the related adult respiratory syndrome (ARDS) have improved mortality and morbidity rates however, there remains a need for improved non-invasive modes of diagnosis and treatment. Currently, there is no accurate method to image and monitor lung inflammation in these patients. The goal of this study was evaluate the performance of the virus-derived peptide, vMIP-II as a tool to detect lung inflammation using positron emission tomography (PET) lung scanning. vMIP-II binds to a known set of chemokine receptors, molecules that orchestrate inflammatory responses by directing specific cell migration to sites of inflammation. We hypothesized that tracking chemokine receptor activity using the vMIP-II probe would enable us to visualize and monitor lung inflammation. In a mouse model of acute lung injury induced by intratracheal lipopolysaccharide (LPS), intravenously administered radionuclide-labeled probe, 64Cu-DOTA-vMIP-II, resulted in a robust and specific PET signal in the lung at 4 and 24 post injury, but not at 48 h and later. Analysis of single cell preparations of lungs from LPS treated mice injected with fluorescently labeled vMIP-II showed a similar high 24 h and diminished 48 h pattern of cell binding, by flow cytometry. Analysis of immune cell populations using identified specific cell populations that bound the vMIP-II probe only in the acute phase of lung injury. We propose that vMIP-II functions as a sensitive reporter of acute lung injury that can be detected using non-invasive imaging to diagnose and monitor lung injury so that therapies can be rationally administrated.

Language

English (en)

Advisor/Committee Chair

Steven L. Brody

Advisor/Committee Chair's Department

Professor of Medicine Pulmonary & Critical Care Medicine