Characterizing the Immunological Role of Pulmonary Stretch Receptors

Fatehi Hassanabad, Mortaza

Characterizing the Immunological Role of Pulmonary Stretch Receptors

dc.contributor.advisor	George Yipp, Bryan
dc.contributor.advisor	Robert Gillrie, Mark
dc.contributor.author	Fatehi Hassanabad, Mortaza
dc.contributor.committeemember	McDonald, Braedon
dc.contributor.committeemember	Altier, Christophe
dc.date	2022-11
dc.date.accessioned	2022-06-24T19:45:29Z
dc.date.available	2022-06-24T19:45:29Z
dc.date.issued	2022-06-14
dc.description.abstract	Breathing 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.	en_US
dc.identifier.citation	Hassanabad, M. F. (2022). Characterizing the Immunological Role of Pulmonary Stretch Receptors (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.	en_US
dc.identifier.doi	http://dx.doi.org/10.11575/PRISM/39855
dc.identifier.uri	http://hdl.handle.net/1880/114772
dc.language.iso	eng	en_US
dc.publisher.faculty	Cumming School of Medicine	en_US
dc.publisher.institution	University of Calgary	en
dc.rights	University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.	en_US
dc.subject	Inflammation	en_US
dc.subject	Host Defense	en_US
dc.subject	Neuroimmunity	en_US
dc.subject	Pulmonary Immunology	en_US
dc.subject.classification	Immunology	en_US
dc.title	Characterizing the Immunological Role of Pulmonary Stretch Receptors	en_US
dc.type	master thesis	en_US
thesis.degree.discipline	Medicine – Medical Sciences	en_US
thesis.degree.grantor	University of Calgary	en_US
thesis.degree.name	Master of Science (MSc)	en_US
ucalgary.item.requestcopy	true	en_US