Date of Award

5-1-2014

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Field of Study

Cell Biology and Genetics

First Advisor

Lisa Hodge

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.

Comments

Schander, Artur, Lymphatic Pump Treatment Enhances the Lymphatic and Immune System and Ameliorates Disease Severity in a Rat Model of Respiratory Infection. Doctor of Philosophy (Cell Biology and Immunology), May 2014, 197 pp., 18 tables, 30 illustrations, bibliography, 279 titles. Available May 2015

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