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Immunomodulation by Endotoxin Tolerance in Murine Models of Inflammation and Bacterial Infection

Immunomodulation by Endotoxin Tolerance in Murine Models of Inflammation and Bacterial Infection

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Prüfsumme: MD5:90682e066e45e481a3920a201c9d130c

LEHNER, Martin Dominik, 2001. Immunomodulation by Endotoxin Tolerance in Murine Models of Inflammation and Bacterial Infection [Dissertation]. Konstanz: University of Konstanz

@phdthesis{Lehner2001Immun-8643, title={Immunomodulation by Endotoxin Tolerance in Murine Models of Inflammation and Bacterial Infection}, year={2001}, author={Lehner, Martin Dominik}, note={Teilw. ersch. in: Infect. Immun. 69:463-471 (2001); J Immunol 166 (8) (2001) in press}, address={Konstanz}, school={Universität Konstanz} }

2011-03-24T17:45:20Z 2001 eng Lehner, Martin Dominik application/pdf Immunomodulation by Endotoxin Tolerance in Murine Models of Inflammation and Bacterial Infection Lipopolysaccharide (LPS) is a potent immune stimulator which induces many of the pathological sequelae observed during systemic Gram-negative infection. The term endotoxin tolerance describes the phenomenon that the toxicity of LPS is attenuated upon repeated LPS-stimulation. Selective downregulation of certain macrophage activities is considered one of the mechanisms underlying LPS tolerance. In the present thesis it was investigated whether lipoteichoic acid, a component of Gram-positive bacteria, induced similar tolerance in vivo and macrophage refractoriness in vitro. In the second part of the thesis the effect of acquired LPS tolerance on host defense against virulent bacteria was studied.<br /><br /><br />1. TNF release by murine macrophages in response to lipoteichoic acid (LTA) is independent of Toll like receptor (TLR) 4 but requires functional TLR2.<br /><br />2. LTA induced macrophage refractoriness similar to LPS in vitro and in vivo.<br /><br />3. LTA and LPS induced cross-desensitization of macrophages in vitro and cross-tolerance in galactosamine-sensitized mice in vivo.<br /><br />4. Paracrine mediators did not suffice to induce cross-desensitization of macrophages in vitro.<br /><br />5. Cytokine production in response to viable Salmonella typhimurium was attenuated in LPS-tolerant mice.<br /><br />6. Induction of LPS tolerance prior to Salmonella typhimurium infection was associated with decreased bacterial load and a prolongal of survival.<br /><br />7. Early but not late phase reduction of bacteria in LPS-tolerant mice depended on the accumulation of PMN in the peritoneal cavity in response to intraperitoneal LPS injections.<br /><br />8. LPS-tolerance was associated with increased PMN counts in blood and tissues and enhanced oxidative burst capacity of the individual PMN. Depletion of PMN prior to infection partially abrogated the survival benefit associated with LPS-tolerance.<br /><br />9. LPS-tolerant mice displayed improved clearance of systemically injected Salmonella typhimurium and enhanced phagocytic activity of the liver.<br /> deposit-license Lehner, Martin Dominik 2011-03-24T17:45:20Z Immunmodulation durch Endotoxintoleranz in Entzündungs- und bakteriellen Infektionsmodellen der Maus

Dateiabrufe seit 01.10.2014 (Informationen über die Zugriffsstatistik)

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