M1/M2 Macrophages: The Arginine Fork in the Road to Health and Disease
Macrophages have unique and diverse functions necessary for survival. And, in humans (and other species), they are the most abundant leukocytes in tissues. The Innate functions of macrophages that are best known are their unusual ability to either "Kill" or "Repair". Since killing is a destructive p...
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2021
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| author | Charles Dudley Mills Laurel L Lenz Klaus Ley |
| author_browse | Charles Dudley Mills Klaus Ley Laurel L Lenz |
| author_facet | Charles Dudley Mills Laurel L Lenz Klaus Ley |
| author_sort | Charles Dudley Mills |
| collection | Directory of Open Access Books |
| description | Macrophages have unique and diverse functions necessary for survival. And, in humans (and other species), they are the most abundant leukocytes in tissues. The Innate functions of macrophages that are best known are their unusual ability to either "Kill" or "Repair". Since killing is a destructive process and repair is a constructive process, it was stupefying how one cell could exhibit these 2 polar – opposite functions. However, in the late 1980’s, it was shown that macrophages have a unique ability to enzymatically metabolize Arginine to Nitric Oxide (NO, a gaseous non – specific killer molecule) or to Ornithine (a precursor of polyamines and collagen for repair). The dual Arginine metabolic capacity of macrophages provided a functional explanation for their ability to kill or repair. Macrophages predominantly producing NO are called M1 and those producing Ornithine are called M2. M1 and M2 – dominant responses occur in lower vertebrates, and in T cell deficient vertebrates being directly driven by Damage and Pathogen Associated Molecular Patterns (DAMP and PAMP). Thus, M1 and M2 are Innate responses that protect the host without Adaptive Immunity. In turn, M1/M2 is supplanting previous models in which T cells were necessary to "activate" or "alternatively activate" macrophages (the Th1/Th2 paradigm). M1 and M2 macrophages were named such because of the additional key findings that these macrophages stimulate Th1 and Th2 – like responses, respectively. So, in addition to their unique ability to kill or repair, macrophages also govern Adaptive Immunity. All of the foregoing would be less important if M1 or M2 – dominant responses were not observed in disease. But, they are. The best example to date is the predominance of M2 macrophages in human tumors where they act like wound repair macrophages and actively promote growth. More generally, humans have become M2 – dominant because sanitation, antibiotics and vaccines have lessened M1 responses. And, M2 dominance seems the cause of ever - increasing allergies in developed countries. Obesity represents a new and different circumstance. Surfeit energy (e.g., lipoproteins) causes monocytes to become M1 dominant in the vessel walls causing plaques. Because M1 or M2 dominant responses are clearly causative in many modern diseases, there is great potential in developing the means to selectively stimulate (or inhibit) either M1 or M2 responses to kill or repair, or to stimulate Th1 or Th2 responses, depending on the circumstance. The contributions here are meant to describe diseases of M1 or M2 dominance, and promising new methodologies to modulate the fungible metabolic machinery of macrophages for better health. |
| format | Online |
| id | doab-20.500.12854ir-52510 |
| institution | Directory of Open Access Books |
| language | eng |
| publishDate | 2021 |
| publishDateRange | 2021 |
| publishDateSort | 2021 |
| publisher | Frontiers Media SA |
| publisherStr | Frontiers Media SA |
| record_format | ojs |
| spelling | doab-20.500.12854ir-525102024-03-31T13:08:17Z M1/M2 Macrophages: The Arginine Fork in the Road to Health and Disease Charles Dudley Mills Laurel L Lenz Klaus Ley R5-920 RC581-607 Infection wound innate immunity M1 M2 Atherosclerosis macrophage Cancer thema EDItEUR::M Medicine and Nursing Macrophages have unique and diverse functions necessary for survival. And, in humans (and other species), they are the most abundant leukocytes in tissues. The Innate functions of macrophages that are best known are their unusual ability to either "Kill" or "Repair". Since killing is a destructive process and repair is a constructive process, it was stupefying how one cell could exhibit these 2 polar – opposite functions. However, in the late 1980’s, it was shown that macrophages have a unique ability to enzymatically metabolize Arginine to Nitric Oxide (NO, a gaseous non – specific killer molecule) or to Ornithine (a precursor of polyamines and collagen for repair). The dual Arginine metabolic capacity of macrophages provided a functional explanation for their ability to kill or repair. Macrophages predominantly producing NO are called M1 and those producing Ornithine are called M2. M1 and M2 – dominant responses occur in lower vertebrates, and in T cell deficient vertebrates being directly driven by Damage and Pathogen Associated Molecular Patterns (DAMP and PAMP). Thus, M1 and M2 are Innate responses that protect the host without Adaptive Immunity. In turn, M1/M2 is supplanting previous models in which T cells were necessary to "activate" or "alternatively activate" macrophages (the Th1/Th2 paradigm). M1 and M2 macrophages were named such because of the additional key findings that these macrophages stimulate Th1 and Th2 – like responses, respectively. So, in addition to their unique ability to kill or repair, macrophages also govern Adaptive Immunity. All of the foregoing would be less important if M1 or M2 – dominant responses were not observed in disease. But, they are. The best example to date is the predominance of M2 macrophages in human tumors where they act like wound repair macrophages and actively promote growth. More generally, humans have become M2 – dominant because sanitation, antibiotics and vaccines have lessened M1 responses. And, M2 dominance seems the cause of ever - increasing allergies in developed countries. Obesity represents a new and different circumstance. Surfeit energy (e.g., lipoproteins) causes monocytes to become M1 dominant in the vessel walls causing plaques. Because M1 or M2 dominant responses are clearly causative in many modern diseases, there is great potential in developing the means to selectively stimulate (or inhibit) either M1 or M2 responses to kill or repair, or to stimulate Th1 or Th2 responses, depending on the circumstance. The contributions here are meant to describe diseases of M1 or M2 dominance, and promising new methodologies to modulate the fungible metabolic machinery of macrophages for better health. 2021-02-11T18:29:04Z 2021-02-11T18:29:04Z 2015-12-03 13:02:24 2015 book 17734 16648714 9782889194995 https://directory.doabooks.org/handle/20.500.12854/52510 eng Frontiers Research Topics image/jpeg Attribution 4.0 International http://www.frontiersin.org/books/M1_M2_Macrophages_The_Arginine_Fork_in_the_Road_to_Health_and_Disease/476 http://journal.frontiersin.org/researchtopic/2317/m1m2-macrophages-the-arginine-fork-in-the-road-to-health-and-disease Frontiers Media SA 10.3389/978-2-88919-499-5 10.3389/978-2-88919-499-5 bf5ce210-e72e-4860-ba9b-c305640ff3ae 9782889194995 280 open access |
| spellingShingle | R5-920 RC581-607 Infection wound innate immunity M1 M2 Atherosclerosis macrophage Cancer thema EDItEUR::M Medicine and Nursing Charles Dudley Mills Laurel L Lenz Klaus Ley M1/M2 Macrophages: The Arginine Fork in the Road to Health and Disease |
| title | M1/M2 Macrophages: The Arginine Fork in the Road to Health and Disease |
| title_full | M1/M2 Macrophages: The Arginine Fork in the Road to Health and Disease |
| title_fullStr | M1/M2 Macrophages: The Arginine Fork in the Road to Health and Disease |
| title_full_unstemmed | M1/M2 Macrophages: The Arginine Fork in the Road to Health and Disease |
| title_short | M1/M2 Macrophages: The Arginine Fork in the Road to Health and Disease |
| title_sort | m1 m2 macrophages the arginine fork in the road to health and disease |
| topic | R5-920 RC581-607 Infection wound innate immunity M1 M2 Atherosclerosis macrophage Cancer thema EDItEUR::M Medicine and Nursing |
| topic_facet | R5-920 RC581-607 Infection wound innate immunity M1 M2 Atherosclerosis macrophage Cancer thema EDItEUR::M Medicine and Nursing |
| url | 17734 |
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