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Published on: August 7, 2018
Cell Death in the Lung: The Apoptosis-Necroptosis Axis
Maor Sauler1, Isabel S Bazan1, Patty J Lee1
1Department of Medicine, Yale School of Medicine, New Haven, Connecticut 06520, USA;
Abstract:
Regulated cell death is a major mechanism to eliminate damaged, infected, or superfluous cells. Previously, apoptosis was thought to be the only regulated cell death mechanism; however, new modalities of caspase-independent regulated cell death have been identified, including necroptosis, pyroptosis, and autophagic cell death. As an understanding of the cellular mechanisms that mediate regulated cell death continues to grow, there is increasing evidence that these pathways are implicated in the pathogenesis of many pulmonary disorders. This review summarizes our understanding of regulated cell death as it pertains to the pathogenesis of chronic obstructive pulmonary disease, asthma, idiopathic pulmonary fibrosis, acute respiratory distress syndrome, and pulmonary arterial hypertension.
Insights
Regulated cell death, including apoptosis and caspase-independent pathways like necroptosis, is crucial for cell elimination. These mechanisms are increasingly linked to the development of major lung diseases.
Area of Science:
- Cell Biology
- Pulmonary Medicine
- Pathogenesis Research
Background:
- Regulated cell death is essential for maintaining tissue homeostasis by eliminating compromised cells.
- Apoptosis was historically considered the primary form of regulated cell death.
- Emerging research has identified alternative caspase-independent regulated cell death pathways, such as necroptosis, pyroptosis, and autophagic cell death.
Purpose of the Study:
- To review the role of various regulated cell death modalities in the pathogenesis of significant pulmonary disorders.
- To consolidate current knowledge on how different cell death mechanisms contribute to lung disease.
Main Methods:
- Literature review of scientific articles and research papers.
- Synthesis of findings on regulated cell death pathways and their involvement in pulmonary diseases.
- Focus on specific conditions: COPD, asthma, IPF, ARDS, and PAH.
Main Results:
- Multiple regulated cell death pathways, beyond apoptosis, are active in lung tissue.
- These pathways play a critical role in the development and progression of various chronic and acute lung conditions.
- Specific examples include the involvement of necroptosis, pyroptosis, and autophagy in diseases like COPD, asthma, IPF, ARDS, and PAH.
Conclusions:
- Regulated cell death pathways are integral to the pathogenesis of major pulmonary diseases.
- Understanding these diverse cell death mechanisms offers potential therapeutic targets for lung disorders.
- Further research into caspase-independent cell death in the lungs is warranted.
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