Understanding the function and behaviour of alveolar macrophages

Neupane, Arpan Sharma

Understanding the function and behaviour of alveolar macrophages

dc.contributor.advisor	Kubes, Paul
dc.contributor.author	Neupane, Arpan Sharma
dc.contributor.committeemember	Mody, Christopher
dc.contributor.committeemember	Chee, Chunmin
dc.contributor.committeemember	D'Cruz, Louise
dc.date	2021-06
dc.date.accessioned	2021-05-07T21:06:57Z
dc.date.available	2021-05-07T21:06:57Z
dc.date.issued	2021-04-28
dc.description.abstract	Humans breathe in more than 10,000 liters of non-sterile air daily. This necessitates a constant interface of the lungs with the outside environment. Importantly, this process can allow pathogens, allergens, or other immunogenic moieties access into the lungs which can lead to injury or inflammation. Interestingly, despite this imminent threat, the lungs in most healthy individuals are kept free of pathogens and inflammation. The mechanisms by which such a feat is accomplished are still being uncovered. One important player in this regard is the resident phagocyte of the alveoli- the alveolar macrophages (AMs). These phagocytic cells have been identified as being crucial in maintaining the alveolar homeostasis. Interestingly, the alveoli have been proposed to outnumber AMs, leading to many alveoli that are devoid of AMs at any given point in time. Importantly, the current literature suggests that AMs, like most tissue resident macrophages, are sessile. If so, the numerical disadvantage could be exploited by pathogens that are breathed in, unless immune cells from the blood stream intervened. However, this would translate to omnipresent and persistent inflammation. Using in vivo real-time intravital imaging of the alveoli, we observed AMs crawling in and between the alveoli using the Pores of Kohn. Importantly, these AMs sensed, chemotaxed (via C5a and FPR1 dependent mechanism) and phagocytosed inhaled bacterial pathogens such as P. aeruginosa and S. aureus, cloaking the bacteria from neutrophils. Impairing AM chemotaxis towards bacteria, induced superfluous neutrophil recruitment leading to inappropriate inflammation and injury of the lungs. Additionally, in disease contexts such as viral infection or LPS mediated inflammation, AM behaviour was markedly altered which led to decreased bacterial capture and increased secondary co-infections. Collectively, the observations made in this thesis elucidate a crucial mechanism by which AMs keep the alveoli free of pathogens and inflammation leading to a significant advancement in the understanding of alveolar macrophage behaviour and function.	en_US
dc.identifier.citation	Neupane, A. S. (2021). Understanding the function and behaviour of alveolar macrophages (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.	en_US
dc.identifier.doi	http://dx.doi.org/10.11575/PRISM/38838
dc.identifier.uri	http://hdl.handle.net/1880/113378
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	Immunology	en_US
dc.subject	alveolar macrophage	en_US
dc.subject	intravital microscopy	en_US
dc.subject.classification	Immunology	en_US
dc.title	Understanding the function and behaviour of alveolar macrophages	en_US
dc.type	doctoral thesis	en_US
thesis.degree.discipline	Medicine – Immunology	en_US
thesis.degree.grantor	University of Calgary	en_US
thesis.degree.name	Doctor of Philosophy (PhD)	en_US
ucalgary.item.requestcopy	false	en_US