Cited by 3,287Immune cells in cancerT-cell and B-cell ImmunologyImmune Response and Inflammation

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M-1/M-2 Macrophages and the Th1/Th2 Paradigm

Mills, Charles D, Kincaid, Kristi, Alt, Jennifer M, Heilman, Michelle J, Hill, Annette M·2000·The Journal of Immunology

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Abstract

Evidence is provided that macrophages can make M-1 or M-2 responses. The concept of M-1/M-2 fomented from observations that macrophages from prototypical Th1 strains (C57BL/6, B10D2) are more easily activated to produce NO with either IFN-gamma or LPS than macrophages from Th2 strains (BALB/c, DBA/2). In marked contrast, LPS stimulates Th2, but not Th1, macrophages to increase arginine metabolism to ornithine. Thus, M-1/M-2 does not simply describe activated or unactivated macrophages, but cells expressing distinct metabolic programs. Because NO inhibits cell division, while ornithine can stimulate cell division (via polyamines), these results also indicate that M-1 and M-2 responses can influence inflammatory reactions in opposite ways. Macrophage TGF-beta1, which inhibits inducible NO synthase and stimulates arginase, appears to play an important role in regulating the balance between M-1 and M-2. M-1/M-2 phenotypes are independent of T or B lymphocytes because C57BL/6 and BALB/c NUDE or SCID macrophages also exhibit M-1/M-2. Indeed, M-1/M-2 proclivities are magnified in NUDE and SCID mice. Finally, C57BL/6 SCID macrophages cause CB6F1 lymphocytes to increase IFN-gamma production, while BALB/c SCID macrophages increase TGF-beta production. Together, the results indicate that M-1- or M-2-dominant macrophage responses can influence whether Th1/Th2 or other types of inflammatory responses occur.

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Background
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Authors: Mills, C. D., Kincaid, K., Alt, J. M., Heilman, M. J., & Hill, A. M.
Affiliations: University of Minnesota (US)
Venue: The Journal of Immunology
Publisher: Oxford University Press (OUP)
Published: 2000-06
Volume: 164
Issue: 12
Pages: 6166-6173
ISSN: 0022-1767 (ISSN-L)
1550-6606
DOI: 10.4049/jimmunol.164.12.6166
OpenAlex: W2163175900
Cited by: 3,287
References: 2
Citations by year: 2026: 159 · 2025: 238 · 2024: 269 · 2023: 253 · 2022: 291 · 2021: 302 · 2020: 258 · 2019: 191 · 2018: 157 · 2017: 156 · 2016: 160 · 2015: 138 · 2014: 115 · 2013: 67 · 2012: 73
FWCI: 8.03
Type: journal article
Language: en
Open access: closed
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations: The Journal of Immunology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5p01gm050150-05, 5r01dk051495-02)
National Institute of General Medical Sciences (5P01GM50150)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK51495)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords: Th1/Th2 balance, nitric oxide, arginine metabolism, ornithine, TGF-β1, inducible nitric oxide synthase, arginase, macrophage activation, interferon-gamma, lipopolysaccharide, polyamines, SCID mice, nude mice
MeSH terms: Animals, Arginine, Cells, Cultured, Female, Lymphocyte Activation, Macrophage Activation, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Nude, Nitric Oxide, Species Specificity, Spleen, Immunophenotyping, Cytokines, Transforming Growth Factor beta, Mice, SCID, Macrophages, Peritoneal, Th1 Cells, Th2 Cells, Coculture Techniques, Mice

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M-1/M-2 Macrophages and the Th1/Th2 Paradigm

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