000			04058naaaa2200361uu 4500
001			https://directory.doabooks.org/handle/20.500.12854/52510
005			20220220054738.0
020			_a978-2-88919-499-5
020			_a9782889194995
024	7		_a10.3389/978-2-88919-499-5 _cdoi
041	0		_aEnglish
042			_adc
100	1		_aCharles Dudley Mills _4auth
700	1		_aLaurel L Lenz _4auth
700	1		_aKlaus Ley _4auth
245	1	0	_aM1/M2 Macrophages: The Arginine Fork in the Road to Health and Disease
260			_bFrontiers Media SA _c2015
300			_a1 electronic resource (280 p.)
506	0		_aOpen Access _2star _fUnrestricted online access
520			_aMacrophages 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.
540			_aCreative Commons _fhttps://creativecommons.org/licenses/by/4.0/ _2cc _4https://creativecommons.org/licenses/by/4.0/
546			_aEnglish
653			_aInfection
653			_awound
653			_ainnate immunity
653			_aM1
653			_aM2
653			_aAtherosclerosis
653			_amacrophage
653			_aCancer
856	4	0	_awww.oapen.org _uhttp://journal.frontiersin.org/researchtopic/2317/m1m2-macrophages-the-arginine-fork-in-the-road-to-health-and-disease _70 _zDOAB: download the publication
856	4	0	_awww.oapen.org _uhttps://directory.doabooks.org/handle/20.500.12854/52510 _70 _zDOAB: description of the publication
999			_c68779 _d68779