Investigating the Reconstitution and Function of Peritoneal Cavity Macrophages after LPS-induced Peritonitis

The tissue-resident macrophages of the peritoneum are sentinel immune cells, in constant motion within the serous fluid of the abdomen. Like most tissue macrophages, the GATA6+ large peritoneal macrophages (LPMs) are responsible for the clearance and removal of pathogens that may break through the defensive barriers of the abdomen. However, upon inflammation incurred by the response of the immune system to foreign matter, the LPM population seemingly disappears and down-regulates its signature cell markers. The aim of this thesis project was to elucidate the fate of the large peritoneal macrophages after stimulation with an inflammatory agent as well as the eventual return of the macrophage resident cell population. This work used genetically engineered, LPM and monocyte-derived fate mapping mice to track the location and re-constitution of the large peritoneal cavity macrophage population after lipopolysaccharide (LPS)-induced peritonitis. A double recombinase, GATA6 and Lyz-M genetically driven fate mapping mouse was engineered to report on the large peritoneal population in response to a biologically relevant dose of lipopolysaccharide. Spectral flow cytometry and confocal whole mount imaging was used to investigate the ‘disappearance’ of LPM from the peritoneal cavity upon stimulation of the noxious agent. After 10 days of LPS administration, the LPM fate mapping mouse and the Ms4a3-monocyte derived reporter mouse were used to illustrate the repopulation of endogenous LPMs and newly recruited monocytes that contribute to the macrophage pool upon resolution of inflammation. My findings suggest that LPMs concentrate and localize at ‘milky spots’ of the omentum. Upon resolution of inflammation, the resident macrophage pool was made up both endogenous GATA6 and bone marrow-derived macrophages.

Name thesis:degree_name

Master of Science (MSc)

Discipline thesis:degree_discipline

Medicine – Immunology

Grantor dc:publisher.institution

Graduate Studies

Year dc:date.issued

2025

Author dc:creator

• Tejada, Oscar Ernesto

Advisor dc:contributor.advisor

• Kubes, Paul

Committee members dc:contributor.committeemember

• Geuking, Markus
• Biernaskie, Jeff
• Cobo, Eduardo

• Peritoneal macrophages
• LPS peritonitis
• GATA6 cavity macrophage
• Fate-mapping
• Omentum
• Bone-marrow derived macrophage

Statement 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.

Language dc:language.iso

en

DOI

https://dx.doi.org/10.11575/PRISM/48453

OAI identifier oai:identifier

oai:ucalgary.scholaris.ca:1880/120847