title: Complement Protein C1q Enhances Macrophage Foam Cell Survival and Efferocytosis.
abstract: In the atherosclerotic lesion, macrophages ingest high levels of damaged modified low-density lipoproteins (LDLs), generating macrophage foam cells. Foam cells undergo apoptosis and, if not efficiently cleared by efferocytosis, can undergo secondary necrosis, leading to plaque instability and rupture. As a component of the innate immune complement cascade, C1q recognizes and opsonizes modified forms of LDL, such as oxidized or acetylated LDL, and promotes ingestion by macrophages in vitro. C1q was shown to be protective in an atherosclerosis model in vivo. Therefore, this study aimed to investigate whether ingestion of modified LDL in the presence of C1q alters macrophage foam cell survival or function. In an unbiased transcriptome analysis, C1q was shown to modulate expression of clusters of genes involved in cell death and apoptosis pathways in human monocyte-derived macrophages ingesting modified LDL; this was validated by quantitative PCR in human and murine macrophages. C1q downregulated levels and activity of active caspase-3 and PARP-1 in human and mouse macrophages during ingestion of modified LDL. This led to a measurable increase in survival and decrease in cell death, as measured by alamarBlue and propidium iodide assays, respectively. C1q opsonization also increased phagocytosis and efferocytosis in macrophage foam cells. These data suggest that C1q promotes macrophage survival during ingestion of excess cholesterol, as well as improves foam cell efferocytic function. This may be important in slowing disease progression and provides insight into the protective role of C1q in early atherosclerosis.
authors.affiliation: Department of Biological Sciences, California State University Long Beach, Long Beach, CA 90840.
authors.forename: Marc C
authors.identifier: 0000-0001-5685-8864
authors.initials: MC
authors.lastname: Pulanco
authors.affiliation: Department of Biological Sciences, California State University Long Beach, Long Beach, CA 90840.
authors.forename: Jason
authors.identifier: 0000-0003-0214-9004
authors.initials: J
authors.lastname: Cosman
authors.affiliation: Department of Biological Sciences, California State University Long Beach, Long Beach, CA 90840.
authors.forename: Minh-Minh
authors.initials: MM
authors.lastname: Ho
authors.affiliation: Department of Biological Sciences, California State University Long Beach, Long Beach, CA 90840.
authors.forename: Jessica
authors.identifier: 0000-0001-5868-5522
authors.initials: J
authors.lastname: Huynh
authors.affiliation: Department of Biological Sciences, California State University Long Beach, Long Beach, CA 90840.
authors.forename: Karina
authors.initials: K
authors.lastname: Fing
authors.affiliation: Department of Biological Sciences, California State University Long Beach, Long Beach, CA 90840.
authors.forename: Jacqueline
authors.identifier: 0000-0002-2144-9654
authors.initials: J
authors.lastname: Turcu
authors.affiliation: Department of Biological Sciences, California State University Long Beach, Long Beach, CA 90840 deborah.fraser@csulb.edu.
authors.forename: Deborah A
authors.identifier: 0000-0003-0375-613X
authors.initials: DA
authors.lastname: Fraser
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D050197:Atherosclerosis / Q000276:immunology / Q000473:pathology; D002470:Cell Survival / Q000276:immunology; D015922:Complement C1q / Q000276:immunology*; D005487:Foam Cells / Q000276:immunology*; D006801:Humans; D051379:Mice; D016133:Polymerase Chain Reaction
chemical_list: D015922:Complement C1q