Autophagy provides a mechanism for the turnover of cellular organelles and proteins through a lysosome-dependent degradation pathway. During starvation, autophagy exerts a homeostatic function that promotes cell survival by recycling metabolic precursors. Additionally, autophagy can interact with other vital processes such as programmed cell death, inflammation, and adaptive immune mechanisms, and thereby potentially influence disease pathogenesis. Macrophages deficient in autophagic proteins display enhanced caspase-1-dependent proinflammatory cytokine production and the activation of the inflammasome. Autophagy provides a functional role in infectious diseases and sepsis by promoting intracellular bacterial clearance. Mutations in autophagy-related genes, leading to loss of autophagic function, have been implicated in the pathogenesis of Crohn's disease. Furthermore, autophagy-dependent mechanisms have been proposed in the pathogenesis of several pulmonary diseases that involve inflammation, including cystic fibrosis and pulmonary hypertension. Strategies aimed at modulating autophagy may lead to therapeutic interventions for diseases associated with inflammation. 1. Introduction 1.1. Inflammation Acute inflammation acts as part of the host’s innate protective response to infection or tissue injury. Endothelial cell injury or microbial infection causes changes in vascular permeability, local edema, and in the distribution of chemoattractants [1, 2]. The activation of endothelial cells allows the transmigration of leukocytes, initially primarily neutrophils (polymorphonuclear (PMN) cells), to the site of tissue injury [3]. Finally, macrophages uptake apoptotic PMN cells, cellular debris, and invasive pathogens via phagocytosis during the resolution of acute inflammation, which leads to neutrophil clearance and the release of anti-inflammatory cytokines such as transforming growth factor-β1. The resolution program ends with the efflux of macrophages from the site of inflammation through lymphatics [4]. However, aberrant inflammatory responses can be associated with a wide range of acute, chronic, and systemic inflammatory disorders, such as cardiovascular disease, asthma, inflammatory bowel disease, rheumatoid arthritis [1], and cystic fibrosis [5]. In recent years, emerging evidence has indicated that the process of macroautophagy may play an essential role for the host during bacterial clearance [6] as well as interact with inflammatory processes, and thereby potentially impact the outcome of disease progression. 1.2. Autophagy Macroautophagy
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