Pulmonary intravascular macrophages (PIMs) promote lung inflammation and are found in ruminants, horses, pigs, cats, and dolphins, but not in primates, rats and mice. Rabbits are used to study mechanisms of lung inflammation in humans, but disagreement exists whether rabbits have PIMs. This study examined rabbits for PIMs, and their influence on endotoxin-induced lung inflammation.<p>
Rabbits were treated with gadolinium chloride (10 mg/kg intravenous: Group GC, n=6) to produce apoptosis in PIMs, or with saline (Group SAL, n=6). Rabbits were euthanized 48 hours later. Light microscopic examination of epoxy-embedded rabbit lung sections revealed mononuclear phagocytes in alveolar septa. Transmission electron microscopy confirmed PIMs with lysosomes and close attachment to capillary endothelium. Light microscopic immuno-cytochemistry using rabbit anti-macrophage antibody (RAM-11) showed staining of septal and alveolar macrophages. There was no difference in number of RAM-11 positive septal cells between SAL and GC rabbits (P=0.2).<p>
Rabbits were administered intravenous E.coli 0127:B8 endotoxin (100 Ýg/kg) 48 hours after GC (GC-LPS; n=5) or SAL treatment (SAL-LPS; n=6), and euthanized 24 hours later. Rabbits in both LPS treated groups were hypocalcaemic and exhibited compensated metabolic acidosis compared to SAL rabbits. Four rabbits died in the SAL-LPS group within 24 hours of the endotoxin treatment and were replaced. None died in the GC-LPS group (Chi-square comparison for survival P=0.063). Greater numbers of septal heterophils were found in groups SAL-LPS and GC-LPS compared to SAL and GC. TNFÑ protein in serum, and IL-1Ò and IL-6 mRNA in lung tissues were increased in SAL-LPS compared to SAL and GC rabbits. Lung tissues from SAL-LPS rabbits but not in GC-LPS showed moderate inflammation, but lung wet/dry ratios were not different. Lung tissue TNFÑ, IL-1Ònand IL-6 mRNA, myeloperoxidase activity, and serum TNFÑ were reduced in GC-LPS animals compared to SAL-LPS. Immuno-electron microscopy revealed TNFÑ in PIMs in normal and LPS-treated rabbits. Lung and liver tissue TNFÑ, IL-8 and MCP-1 protein concentrations were not different between groups. GC did not appear to reduce liver inflammation. These data show that rabbits have low numbers of PIMs. GC treatment induced apoptosis in PIMs and reduced endotoxin-induced lung inflammation and mortality.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:SSU.etd-02092010-141034 |
| Date | 24 February 2010 |
| Creators | Duke, Tanya |
| Contributors | Singh, Baljit, Townsend, Hugh, Hiebert, Linda, Simko, Elemir |
| Publisher | University of Saskatchewan |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://library.usask.ca/theses/available/etd-02092010-141034/ |
| Rights | unrestricted, 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 Saskatchewan 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. |
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