رسالة جامعية
LEUKOCYTE-DERIVED EXTRACELLULAR SUPEROXIDE DISMUTASE IN PULMONARY DISEASE
| العنوان: | LEUKOCYTE-DERIVED EXTRACELLULAR SUPEROXIDE DISMUTASE IN PULMONARY DISEASE |
|---|---|
| المؤلفون: | Manni, Michelle Lynn |
| مرشدي الرسالة: | Wendy M. Mars, PhD, Carol A. Feghali-Bostwick, PhD, Tim D. Oury, MD, PhD, Jon D. Piganelli, PhD, Bruce A. Freeman, PhD, Charleen T. Chu, MD, PhD |
| بيانات النشر: | University of Pittsburgh, 2011. |
| سنة النشر: | 2011 |
| المجموعة: | University of Pittsburgh |
| Original Material: | http://etd.library.pitt.edu/ETD/available/etd-02282011-105626Test/ |
| مصطلحات موضوعية: | Cellular and Molecular Pathology |
| الوصف: | The antioxidant enzyme extracellular superoxide dismutase (EC-SOD) is abundant in the lung and limits inflammation and tissue injury in response to many pulmonary insults. Previous studies reported a loss of full-length EC-SOD from the lung parenchyma with accumulation of proteolyzed EC-SOD in the airspace after interstitial lung injury. However, following airspace only inflammation (pneumonia), EC-SOD accumulates in the airspace without a loss from the interstitium, suggesting this antioxidant may be released from an extrapulmonary source. Because leukocytes are known to express EC-SOD and are prevalent in the bronchoalveolar lavage fluid after injury, it was hypothesized that these cells may transport and release EC-SOD into airspaces. To investigate this, bone marrow chimeras were generated using wild-type and EC-SOD knockout (KO) mice. Following intratracheal treatment with asbestos, reconstituted mice without pulmonary EC-SOD expression, but with EC-SOD in infiltrating and resident leukocytes did not have detectable levels of EC-SOD in the airspaces. In addition, leukocytederived EC-SOD did not significantly lessen inflammation or early stage fibrosis. Although these results indicate that leukocyte-derived EC-SOD is not influential in asbestos-induced interstitial lung injury, EC-SOD in these cells may play a role in attenuating pneumonias and other inflammatory diseases. To test this hypothesis, wild-type and EC-SOD KO mice were given Escherichia coli pneumonia. Notably, even though EC-SOD KO mice had greater pulmonary inflammation than wild-type mice, there was less bacterial clearance from their lungs following infection. While EC-SOD expression has been previously reported in macrophages and neutrophils, its function and subcellular localization in these inflammatory cells is unclear. In this study, EC-SOD was found to be in membrane bound vesicles of phagocytes. This finding led to the hypothesis that inflammatory cell EC-SOD may play a role in antibacterial defense. To investigate this, phagocytes from wild-type and EC-SOD KO mice were evaluated. While macrophages lacking EC-SOD produced more oxidants than EC-SOD expressing cells after stimulation, they had significantly impaired phagocytosis and bacterial killing ability. Overall, these studies suggest that while EC-SOD inside leukocytes does not contribute to interstitial lung injuries, it plays a central role in mediating bacterial infections by facilitating bacterial clearance and limiting inflammation by promoting phagocytosis. |
| Original Identifier: | oai:PITTETD:etd-02282011-105626 |
| نوع الوثيقة: | text |
| وصف الملف: | application/pdf |
| اللغة: | English |
| الإتاحة: | http://etd.library.pitt.edu/ETD/available/etd-02282011-105626Test/ |
| حقوق: | restricted I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
| رقم الانضمام: | edsndl.PITT.oai.PITTETD.etd.02282011.105626 |
| قاعدة البيانات: | Networked Digital Library of Theses & Dissertations |
| الوصف غير متاح. |