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Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
Control of Macrophage Dynamics as a Potential Therapeutic Approach for Clinical Disorders Involving Chronic
Wakana Ohashi1, Kohshi Hattori1, Yuichi Hattori2
1Department of Molecular and Medical Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan (W.O., Y.H.); and Department of Anesthesiology and Pain Relief Center, University of Tokyo Hospital, Tokyo, Japan (K.H.).
Abstract:
Macrophages are a well recognized player of both innate and adaptive immunity and have emerged as a key regulator of systemicmetabolism, hematopoiesis, vasculogenesis, apoptosis, malignancy, and reproduction. Such pleiotropic roles of macrophages are mirrored by their protean features. Upon environmental. challenges, macrophages redistribute and differentiate in situ and contribute to the multiple disease states by exerting protective and pathogenic effects. The environmental challenges include cytokines, chemokines, lipid mediators, and extrinsic insults, such as food and pathogenic bacteria. In addition, homeostasis and the activation state of macrophages are influenced by various metabolites from a commensal microbe that colonizes epithelial and mucosal surfaces, such as the lungs, intestines, and skin. In this review, we describe macrophage differentiation, polarization, and various functions in chronic disease states, including chronic inflammatory bowel disease, tumorigenesis, metabolism and obesity, and central nervous system demyelinating disorders. Controlling the macrophage dynamics to affect the pathologic states is considered to be an important therapeutic approach for many clinical disorders involving chronic inflammation.
Insights
Macrophages are crucial immune cells regulating metabolism and disease. Understanding their environmental responses and functions in chronic conditions like IBD and cancer offers therapeutic potential.
Area of Science:
- Immunology and Metabolism
- Cell Biology
- Pathophysiology
Background:
- Macrophages are versatile immune cells involved in innate and adaptive immunity.
- They play critical roles in systemic processes including metabolism, hematopoiesis, and reproduction.
- Macrophage functions are highly adaptable, responding to environmental cues and contributing to both protective and pathogenic effects in disease.
Purpose of the Study:
- To review macrophage differentiation, polarization, and functions in chronic disease states.
- To highlight the influence of environmental factors and microbial metabolites on macrophage homeostasis.
- To discuss the therapeutic potential of modulating macrophage dynamics in chronic inflammatory disorders.
Main Methods:
- Literature review of macrophage biology and function.
- Analysis of macrophage roles in inflammatory bowel disease, tumorigenesis, metabolic disorders, and CNS demyelinating diseases.
- Synthesis of information on environmental influences and therapeutic strategies.
Main Results:
- Macrophages exhibit diverse functions influenced by environmental challenges like cytokines, lipids, and microbial metabolites.
- Macrophage polarization and differentiation are key to their roles in chronic inflammatory conditions.
- Dysregulated macrophage activity contributes significantly to diseases such as IBD, cancer, obesity, and neuroinflammation.
Conclusions:
- Modulating macrophage behavior is a promising therapeutic strategy for numerous chronic inflammatory diseases.
- Understanding macrophage plasticity is essential for developing targeted treatments.
- Further research into macrophage-microbe interactions could yield novel therapeutic avenues.
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