Inflammatory effects of bacterial endotoxins

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Title Inflammatory effects of bacterial endotoxins
Publication Type dissertation
School or College School of Medicine
Department Pathology
Author Neilsen, Paul O.
Date 1999-12
Description At the dawn of the millennium, bacteria remain a significant threat to human health. Worldwide the toll is enormous, including developed countries like the United States, where there are 500,000 cases of sepsis (a serious disease due to bacterial infection) per year with a mortality rate around 40 percent. It has been appreciated in the last several decades that the human inflammatory response to bacteria causes much of the pathology associated with bacterial diseases. Systemic inflammation may originate in tissues as a small infection with localized inflammation before developing into serious bacterial infections and sepsis. A better understanding of the cellular and molecular details of localized inflammation could potentially lead to better models of bacterial disease, prevent serious disease from developing, and ultimately improved therapies for treating patients. The goal of my thesis research project was to better understand the cells and molecules important for an inflammatory response to bacteria. In this thesis I used isolated human cells to model localized acute inflammation in response to synthetic and purified bacterial endotoxins. I found that bacterial endotoxins modified with an N-terminal triacyl-cystein moiety (bacterial lipoproteins and lipopeptides) activated endothelial cells, neutrophils, monocytes, and platelets. These activities were similar in some ways to cellular activation by the prototypic bacterial endotoxin, lipopolysaccharide, but were also distinct in other important ways. For example, bacterial lipoproteins and lipopeptide activation of endothelial cells and neutrophils were less dependant on serum and serum proteins than was lipopolysaccharide. These differences are important because inflammation generated by lipopolysaccharide has been thought to represent Grain-negative bacterial infections. In addition, I demonstrated that the major lipoprotein purified from E. coli was proinflammatory in a mouse-model of lung inflammation; demonstrating that triacyl-cystein modified bacterial lipoproteins are potent initiators of inflammation both in vitro and in vivo. My hope is that the work accomplished in this thesis will bring attention to an important class of bacterial endotoxins that have mostly been overlooked. This increased attention will help build models of bacterial infections and syndromes that better mimic human diseases with the ultimate goal of improving therapies and survival for people with bacterial diseases.
Type Text
Publisher University of Utah
Subject Inflammation; Endotoxins; Bacterial toxins
Subject MESH Inflammation; Endotoxins; Bacterial Toxins
Dissertation Institution University of Utah.
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of "Inflammatory effects of bacterial endotoxins Spencer S. Eccles Health Sciences Library.
Rights Management © Paul O. Neilsen.
Format application/pdf
Format Medium application/pdf
Format Extent 2,001,141 bytes
Identifier undthes,4010
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available)
Master File Extent 2,001,184 bytes
ARK ark:/87278/s66t0pd9
Setname ir_etd
ID 190790
Reference URL https://collections.lib.utah.edu/ark:/87278/s66t0pd9
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