Abstract

In spaceflight, astronauts will be exposed to several environmental risk factors that may lead to disturbances in homeostasis maintained by the central nervous system (CNS) and immune system. Low Earth orbit (LEO) spaceflight studies have shown that microgravity changes virtually all immune parameters that have been evaluated. Similarly, ground based studies have shown that low-dose radiation can also significantly impact immune function. Finally, as most spacecrafts are ecologically and environmentally closed systems, astronauts may be at increased risk for exposure to aerosolized infectious agents. The hypothesis of this study is: Exposure to spaceflight environment (microgravity and radiation) can influence immune responses by upregulation of innate immune responses, altering cytokine expression and ultimately influencing CNS-immune communication.

To elucidate the effects of the inertial aspects of the spaceflight environment on ex vivo inflammatory responses in mice flown on the Space Shuttle Endeavour for 13 days, we characterized several parameters including lymphoid organ masses, splenic leukocyte population distributions, in vitro cytokine secretion patterns and proliferative response to a B cell mitogen, and reactive oxygen species (ROS) scavenging gene expression. We next investigated the effects of low-dose radiation on the response to a live pathogen. Mice were exposed to 3 Gray (Gy) whole-body proton radiation and were inoculated with Escherichia coli (E. coli). Changes in leukocyte populations, cytokine secretions, phagocytic activity, bacteria clearance, Major histocompatibility complex class II (MHC II) expression and cFos in the paraventriculuar nucleus (PVN) were characterized. We then examined the effects of body-only proton radiation exposure on phagocytic activity to determine the role played by immune-CNS communication in radiation-induced changes using a series of assays similar to those used in the whole-body radiation study.

Depression in leukocyte populations and changes in cytokine secretion patterns were noted after exposure to each environmental factor. Our findings also demonstrate an increase in innate immune response, reduced signaling from periphery to CNS and increase in ROS levels. Collectively, our data suggest that spaceflight related stressors can pose a serious health risk to astronauts. These changes could potentially inhibit the adaptive immune response to pathogens, compromising appropriate mechanisms of pathogen clearance. Increases in inflammatory responses, if prolonged can potentially lead to tissue damage and cause chronic inflammatory diseases.

LLU Discipline

Biochemistry

Department

Biochemistry

School

Graduate Studies

First Advisor

Michael J. Pecaut

Second Advisor

Denise L. Bellinger

Third Advisor

Penelope Duerken-Hughes

Fourth Advisor

Monika R. Fleshner

Fifth Advisor

Daila S. Gridley

Degree Name

Doctor of Philosophy (Medical Science)

Degree Level

Ph.D.

Year Degree Awarded

2009

Date (Title Page)

6-2009

Language

English

Library of Congress/MESH Subject Headings

Phagocytosis; Space Flight. Animals; Mice; Extraterrestrial Environment; Weightlessness; Environmental Exposure; Whole--Body Irradiation; Dose-Response Relationship, Radiation. Immune System -- radiation effects; Immune System Processes; Neural Pathways -- physiology; Sympathetic Nervous System; Receptors, Cytokine -- physiology; Reactive Oxygen Species; Escherichia coli -- cytology; Retrospective Studies.

Type

Dissertation

Page Count

xx; 152

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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