Unpublished PhD thesis, University of North Texas Health Science Center, 2014/05, 197, type of study: ,ani,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,

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Keywords:

animal experiment [68]
immune system [53]
lymphatic pump technique [43]
lymphatic system [58]
respiratory infection [11]

Abstract:

The purpose of these studies was to explore the benefits, effects, and mechanisms of LPT in both a healthy and a diseased animal model, and hence provide scientific rationale for the clinical application of LPT. Novel findings in this dissertation demonstrate that in anesthetized canines: 1) LPT mobilizes leukocytes from the GALT into lymphatic circulation; 2) LPT mobilizes inflammatory mediators into lymphatic circulation; and 3) repeated application of LPT increases lymph flow, concentration of leukocytes, and flux of inflammatory mediators into lymphatic circulation. In addition, this dissertation for the first time demonstrates: 1) the development of a novel lymph enhancing rodent model, in which LPT increases leukocyte flux in the cisterna chili, predominantly from the GALT; and 2) that LPT facilitates the clearance of pneumococcal respiratory infection and suggests a mechanism by which LPT might facilitate the clearance of pneumococcal pneumonia. Our studies demonstrated that LPT transiently mobilized leukocytes from the mesenteric lymph nodes. We found a significant increase in the concentrations of MCP-1 and flux of IL-6 flux in TDL and MDL in anesthetized dogs. Interestingly, both IL-6 and MCP-1 were present in BALF of rats infected with pneumococcus, and LPT significantly increased IL-6 and moderately increased MCP-1 concentrations compared to Sham and Control animals, which supports our notion that LPT may increase cytokine/chemokine redistribution from the mesentery to the lung. We demonstrated that LPT enhanced the clearance of S. pneumoniae after 3 consecutive daily treatments and found that LPT increased the concentrations of SP-D, IL-6, IL-12p70, and IL-17 in BALF and enhanced the release of NO2- and IL-6 by AM 4 days post-infection. Collectively these studies suggest, that LPT re-distributes inflammatory mediators to the lung, enhances the recruitment of macrophages and neutrophils to the lung and skews alveolar macrophages towards a M1 phenotype, all of which may be responsible for and promote the clearance of S. pneumoniae.