Characterizing the Immunological Role of Pulmonary Stretch Receptors
AdvisorGeorge Yipp, Bryan
Robert Gillrie, Mark
AuthorFatehi Hassanabad, Mortaza
Committee MemberMcDonald, Braedon
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AbstractBreathing and the resulting exchange of oxygen and carbon dioxide are normally accomplished by pressure changes within the lungs. As we inhale, chest and diaphragm muscles increase the size of our chest cavity, in turn expanding our lungs. This increase in lung volume results in a pressure gradient whereby air from higher pressure areas (i.e. the atmosphere) flows into and fills our lungs, which are at a lower pressure. Exhalation follows the reverse of this process, and so, our bodies effortlessly carry out this vital function more than 20,000 times per day. Lungs contain receptors that are highly sensitive to mechanical stimuli such as pressure changes, cyclic strain, and shear flow. Such receptors are especially relevant to the lung as it is an organ that is frequently exposed to mechanical forces during breathing. This diverse group of molecules, also known as mechanoreceptors, can be found on sensory neurons, epithelium, leukocytes, and numerous other tissues; however, their functions in the lung during infections and inflammation remain obscure. One such mechanosensitive ion channel is TRPV4 which is evolutionarily conserved across all mammalian species and has become increasingly associated with immunological function in recent years. In this body of work, we investigated how mechanoreceptors (and more specifically TRPV4) modify the pulmonary immune response during host defense and inflammation. We have found that mechanical forces affect lung architecture, capillary barrier function, and bacterial dissemination in our rodent models. Moreover, inhibiting TRPV4 using commercially available agents reduces mortality and improves clinical sickness scores during Staphylococcus aureus pneumonia. We have also observed improved immune cell viability and altered neuropeptide levels using these same compounds suggesting that there may be additional neuroimmune mechanisms at play. These findings enhance our current understanding of lung mechanoreceptors and may be useful for identifying future pharmacological interventions during bacterial pneumonia.
CitationHassanabad, M. F. (2022). Characterizing the Immunological Role of Pulmonary Stretch Receptors (Unpublished master's thesis). University of Calgary, Calgary, AB.
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