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Document Type

Thesis - University Access Only

Award Date

2012

Degree Name

Master of Science (MS)

Department

Chemistry and Biochemistry

First Advisor

Adam D. Hoppe

Abstract

Phagocytosis by macrophages is critical for defense against extracellular pathogens. While the phagocytic machinery for Fe-mediated phagocytosis is well characterized, our understanding of particle capture via binding to the Fey receptor is poor. The Fey receptors are a family of single-pass transmembrane receptors with variable affinity for IgG. Initiation of signaling through these receptors is mediated by clustering in response to particle-associated IgG. A growing body of evidence implicates the cytoskeleton as a regulator of transmembrane receptor motion. This work suggests that actiri may influence particle binding and the initiation of Fe receptor signaling. Macrophage Colony Stimulating Factor (MCSF or CSF-1), a macrophage growth factor and chemo-attractant has been implicated as a regulator of phagocytosis. Early work suggested that MCSF regulated phagocytosis by increasing Fe receptor expression. Here, we demonstrate that MCSF is able to transiently increase macrophage phagocytic capacity through independent of receptor expression. Three possible mechanisms were investigated: changes in receptor diffusion, enhancement of membrane convection, or allostery-induced changes in receptor affinity. Actin disruption by drug treatment or fixation prevents MCSF enhancement of capture. MCSF transiently increased protrusive activity of the macrophage plasma membrane without increasing the rate of receptor diffusion, suggesting a model in which MCSF increases particle engagement by stimulation of micro-probing of the local environment. Furthermore, a novel biophysical mechanism for inter-receptor sensitization mediated by the actin cytoskeleton is proposed.

Library of Congress Subject Headings

Phagocytosis
Macrophages
Immunology

Description

Includes bibliographical references (pages 41-44)

Format

application/pdf

Number of Pages

51

Publisher

South Dakota State University

Rights

In Copyright - Non-Commercial Use Permitted
http://rightsstatements.org/vocab/InC-NC/1.0/

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