Dissertation/Thesis Abstract

Complement Protein C1q Modulation of the Macrophage Foam Cell Lipidome
by Pulanco, Marc Christopher V., M.S., California State University, Long Beach, 2018, 59; 10826305
Abstract (Summary)

Recent studies suggest that C1q plays a protective role in early atherosclerosis. C1q directly opsonizes targets including modified low-density lipoproteins leading to increased macrophage foam cell phagocytosis, survival, and efflux. Since cholesterol efflux and survival are often associated with activation of the liver X receptor (LXR) pathway in macrophages, we investigated modulation of LXR activity by C1q. C1q significantly increases macrophage foam cell survival in human monocyte-derived macrophages (HMDM) model in vitro. Using an LXR reporter gene construct in THP-1 macrophages, the data show that after 3 and 24 hours, C1q significantly increases LXR activation in macrophages ingesting highly oxidized LDL. To determine the potential lipid species involved in activation of the LXR, we performed lipidomic analysis by mass spectrometry in THP-1 macrophage and HMDM foam cells. These data suggest that C1q alters the production and secretion of specific LXR-activating lipids such as 25-hydroxycholesterol (25-OHC) and 24-hydroxycholesterol (24-OHC). C1q also increases gene expression of cholesterol 25-hydroxylase which generates 25-OHC in THP-1 macrophages and HMDM. Enhancement of cell survival by C1q was lost in LXRα/β knockdown HMDM foam cells. The presented data suggest that C1q modulation of LXR activation through generation of 25-OHC and 24-OHC enhances macrophage foam cell survival. This may be an important mechanism by which our innate immune system delays the progression of atherosclerosis.

Indexing (document details)
Advisor: Fraser, Deborah A.
Commitee: Gharakhanian, Editte, Narayanaswami, Vasanthy
School: California State University, Long Beach
Department: Biological Sciences
School Location: United States -- California
Source: MAI 58/01M(E), Masters Abstracts International
Source Type: DISSERTATION
Subjects: Biology
Keywords:
Publication Number: 10826305
ISBN: 9780438419889
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