Year: 2018
Type: dissertation
Abstract: Macrophages are able to recognize, bind and internalize pathogens through two types of phagocytic receptors; the Fc receptors (FcγR) and the complement receptors (CR). FcγRs have prevailed to be more pro-inflammatory than CRs in the literature. Our lab wanted to revisit this paradigm and elucidate the signalling mechanism responsible for upregulating cytokine production when opsonic receptors are activated. In this thesis, we show that CR-mediated phagocytosis leads to higher mRNA levels of TNF, IL-1β, IL-6, MMP9 and iNOS than FcγRmediated phagocytosis. Further investigation into the signaling mechanism showed that there is higher NF-κB activation in CR-mediated phagocytosis than FcγR-mediated phagocytosis. We investigated the role of calpain during phagocytosis and our qPCR data shows that the addition of PD 150606, a calpain inhibitor, reduces cytokine expression levels in CR-mediated phagocytosis. Our findings suggests that the upregulation of pro-inflammatory mediators during CR-mediated phagocytosis, in macrophages, maybe dependent upon calpain-mediated activation of NF-κB.
Source: TSpace (University of Toronto)
Author: Durga Acharya
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2943111210