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Updated: Jun 29, 2025
Experimental Analysis of Apoptotic Thymocyte Engulfment by Macrophages
Published on: May 24, 2019
The dance of macrophage death: the interplay between the inevitable and the microenvironment
Magdalena Makuch1, Mariia Stepanechko1, Małgorzata Bzowska1
1Department of Immunology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Kraków, Poland.
Abstract:
Macrophages are highly plastic cells ubiquitous in various tissues, where they perform diverse functions. They participate in the response to pathogen invasion and inflammation resolution following the immune response, as well as the maintenance of homeostasis and proper tissue functions. Macrophages are generally considered long-lived cells with relatively strong resistance to numerous cytotoxic factors. On the other hand, their death seems to be one of the principal mechanisms by which macrophages perform their physiological functions or can contribute to the development of certain diseases. In this review, we scrutinize three distinct pro-inflammatory programmed cell death pathways - pyroptosis, necroptosis, and ferroptosis - occurring in macrophages under specific circumstances, and explain how these cells appear to undergo dynamic yet not always final changes before ultimately dying. We achieve that by examining the interconnectivity of these cell death types, which in macrophages seem to create a coordinated and flexible system responding to the microenvironment. Finally, we discuss the complexity and consequences of pyroptotic, necroptotic, and ferroptotic pathway induction in macrophages under two pathological conditions - atherosclerosis and cancer. We summarize damage-associated molecular patterns (DAMPs) along with other microenvironmental factors, macrophage polarization states, associated mechanisms as well as general outcomes, as such a comprehensive look at these correlations may point out the proper methodologies and potential therapeutic approaches.
Insights
Macrophages utilize programmed cell death pathways like pyroptosis, necroptosis, and ferroptosis for physiological functions and disease development. Understanding these interconnected pathways in macrophages offers therapeutic insights.
Area of Science:
- Immunology and Cell Biology
- Investigating programmed cell death mechanisms in macrophages.
Background:
- Macrophages are versatile immune cells crucial for tissue homeostasis and inflammation.
- While generally resilient, macrophage death is vital for physiological functions and disease pathology.
- Specific programmed cell death pathways play significant roles in macrophage biology.
Purpose of the Study:
- To review three pro-inflammatory programmed cell death pathways in macrophages: pyroptosis, necroptosis, and ferroptosis.
- To explore the dynamic changes and interconnectivity of these cell death pathways within macrophages.
- To discuss the implications of these pathways in atherosclerosis and cancer.
Main Methods:
- Literature review focusing on programmed cell death in macrophages.
- Analysis of the interplay between pyroptosis, necroptosis, and ferroptosis.
- Examination of microenvironmental factors, macrophage polarization, and associated mechanisms.
Main Results:
- Macrophage programmed cell death pathways are interconnected, forming a flexible system responding to microenvironmental cues.
- These pathways are implicated in both physiological macrophage functions and the pathogenesis of diseases like atherosclerosis and cancer.
- Damage-associated molecular patterns (DAMPs) and macrophage polarization states influence cell death outcomes.
Conclusions:
- Understanding the coordinated nature of macrophage cell death pathways is crucial.
- Targeting pyroptosis, necroptosis, and ferroptosis in macrophages presents potential therapeutic strategies for diseases.
- Further research into these pathways can refine diagnostic and therapeutic methodologies.
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