Mechanisms of Macrophage-Directed Inflammation Resolution

• Main Author: Dehn, Shirley
• Format: Dissertation
• Language: English
• Published: ProQuest Dissertations & Theses 01-01-2017
• Subjects: Immunology; Molecular biology
• ISBN: 9780355296921; 0355296926

Efferocytosis is the anti-inflammatory removal of dying cells and cellular debris, occurring billions of times per person, per day as a part of homeostatic maintenance during natural cell turnover. Macrophages are major professional phagocytes of the immune system and are responsible for dead cell clearance during infection and injury. During apoptotic cell uptake, macrophages are reprogrammed to a “resolving” phenotype that limits the production of inflammatory cytokines and increases the release of reparative mediators. In this way, efferocytosis is a process of inflammation resolution and an important modulator of tissue repair. During sterile inflammation, such as Myocardial Infarction (MI), macrophages and their monocyte precursors are recruited to the site of damage where there is limited oxygen tension. It is unclear how these hypoxic environments impact monocyte/macrophage efferocytosis, and downstream repair mechanisms in the context of heart failure. In these chapters we demonstrate (1) a model of Hypoxia Inducible Factor (HIF) regulation of efferocytosis receptor expression in resting macrophages and (2) how monocyte clearance of dying cardiomyocytes orchestrates tissue repair in the healing myocardium during MI. Collectively these data suggest that efferocytosis is a major regulator of wound healing, and factors that modulate efferocytosis efficiency provide understanding into the mechanisms behind inflammation resolution in the heart.