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Find Publications
Theses, dissertations and research publications (including journal articles, conference abstracts and books) from Lund University are collected in this database. Where possible, the option to download a full text document is available. It is also possible to search for Lund University student theses in the student theses database.
| Title | Adhesive and signaling mechanisms in abdominal sepsis |
| Author/s | Su Zhang |
| Department/s |
Department of Clinical Sciences, Malmö
|
| Full-text | Available as PDF |
| Defence date | 2012-05-24 |
| Defence time | 13:00 |
| Defence place | CRC Aula, Entrance 72, Skåne University Hospital, Malmö |
| Opponent | Mihaly Boros |
| Publication/Series | Lund University, Faculty of Medicine Doctoral Dissertation Series |
| Publishing year | 2012 |
| Volume | 2012:44 |
| Pages | 138 |
| Document type | Dissertation |
| Language | English |
| Publisher | Section for Surgery, Clinical Sciences, Malmö |
| Abstract English | Sepsis is a major cause of mortality in intensive care units despite decades of scientific efforts. The lung is recognized as the most sensitive and critical organ affected by the hyper-inflammatory response in septic patients. Immune cell dysfunction develops in later phases of sepsis making patients susceptible to infections. The aim of this dissertation was to reveal pro- and anti-inflammatory mechanisms in abdominal sepsis induced by cecal ligation and puncture (CLP). It was found that immunoneutralization of LFA-1 or Mac-1 not only reduced neutrophil infiltration but also protected against sepsis-caused lung damage. We observed that HMG-CoA reductase inhibitor regulates pulmonary accumulation of neutrophils via antagonizing CD40 ligand secretion from platelets and via decreasing CXC chemokine formation in the lung. Moreover, HMG-CoA reductase inhibition maintained CD4 T-cell function in spleen by reducing apoptosis and by improving proliferation as well as by preserving the ability to produce IFN-γ in the spleen. Moreover, inhibition of HMG-CoA reductase decreased sepsis-induced generation of regulatory T-cells. HMG-CoA reductase inhibitor abolished CLP-evoked increase in the plasma levels of HMGB1 and IL-6. In addition, it was noted that NFAT was activated after induction of sepsis, which was found to regulate pulmonary neutrophil recruitment and tissue damage, systemic inflammation, as well as T-cell dysfunction in abdominal sepsis. Thus, these results identify adhesive and signaling mechanisms, which are of particular importance in modulating septic lung injury and immunosuppression. Data from this thesis may pave the way for developing more specific and effective therapies for patients with abdominal sepsis. |
| Subject |
Medicine and Health Sciences |
| Keywords | lung, abdominal sepsis, infection, neutrophil, chemokines, T-cells, HMG-CoA reductase, NFAT |
| ISBN/ISSN/Other |
ISSN: 1652-8220 ISBN: 978-91-87189-06-7 |
| Supervisor | Henrik Thorlacius |
| Supervisor | Bengt Jeppsson |
| Part of | LFA-1 AND MAC-1 MEDIATE PULMONARY RECRUITMENT OF NEUTROPHILS AND TISSUE DAMAGE IN ABDOMINAL SEPSIS. |
| Part of | Simvastatin antagonizes CD40L secretion, CXC chemokine formation, and pulmonary infiltration of neutrophils in abdominal sepsis. |
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