Bovine respiratory disease complex is the most common disease that causes sig-nificant economic loss, typically in feedlot cattle. Current treatment methods are focused on reducing inflammatory responses, control of airway reactivity and improvement of pulmonary functions without potential side effects. Neutrophils are the key contributors in acute lung inflammation. However, activated neutrophils live longer and cause exces-sive tissue damage upon migration into lungs. Therefore, modulation of their migration and lifespan are attractive approaches in treatment strategies of bovine respiratory dis-ease. Nanotechnology holds significant potential to design new compounds by our ability to manipulate at the nanoscale. Helical rosette nanotubes are a class of novel, biologi-cally inspired, water soluble and metal-free nanotubes. I used helical rosette nanotubes conjugated to arginine-glycine-aspartic acid (RGD-RNT) to study their effects on neu-trophil chemotaxis, cell signaling and apoptosis. Bovine neutrophils exposed to 5% RGD-RNT reduced their migration in response to fMLP (formyl-Methionyl-Leucyl-Phenylalanine), compared to the non-treated group (P<0.001). This inhibitory effect was the same as that of groups treated with ERK1/2 inhibitor (UO126) and p38 MAPK in-hibitor (SB239063). In addition, the phosphorylated ERK1/2 and p38 MAPK for the first time were quantified by sandwich ELISA to elucidate the mechanism of neutrophil mi-gration. The phosphorylation of both the ERK1/2 and p38 was inhibited at 5 minutes by RGD-rosette nanotubes (P<0.05). Furthermore, integrin ÑvÒ3 is possibly involved in mi-gration of bovine neutrophils. Moreover, RGD-RNT did not induce apoptosis of bovine neutrophils which was inversed by pre-exposing them to LPS for 30 minutes (P<0.001). These experiments provide the first evidence that RGD-rosette nanotubes suppress phos-phorylation of ERK1/2 and p38 MAPK and inhibit chemotaxis of bovine neutrophils.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:SSU.etd-12302008-134552 |
| Date | 12 January 2009 |
| Creators | Minh Hong Anh, Le |
| Contributors | Singh, Baljit |
| 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-12302008-134552/ |
| Rights | 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 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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