Macrophages are a diverse group of white blood cells known for eliminating pathogens through phagocytosis. In the past, macrophages were classified by the organ in which they were found: Kuppfer cells in the liver, Langerhans cells in the skin, microglia in the brain and spinal cord, osteoclasts in the bone.

Scientists continue to debate whether macrophages originate in each organ or migrate there from the bone marrow. To clear up some of this debate, the current taxonomy has shifted away from organ-specific macrophages to M1 and M2 macrophages.

Defining M1 and M2 Macrophages

This classification is based upon macrophage polarization rather than macrophage location.

M1 macrophages are classically activated, typically by IFN-γ or lipopolysaccharide (LPS), and produce proinflammatory cytokines, phagocytize microbes, and initiate an immune response. M1 macrophages produce nitric oxide (NO) or reactive oxygen intermediates (ROI) to protect against bacteria and viruses.

M2 macrophages are alternatively activated by exposure to certain cytokines such as IL-4, IL-10, or IL-13. M2 macrophages will produce either polyamines to induce proliferation or proline to induce collagen production. These macrophages are associated with wound healing and tissue repair.

There are three types of M2 macrophages: M2a, M2b, and M2c. Click here to learn more.

M1 and M2 macrophages defined

Source: Tamás Rőszer, “Understanding the Mysterious M2 Macrophage through Activation Markers and Effector Mechanisms,” Mediators of Inflammation, vol. 2015, Article ID 816460, 16 pages, 2015. doi:10.1155/2015/816460

M2 macrophages also contribute to the formation of extracellular matrix and do not produce nitric oxide or present antigen to T cells. Tumor-infiltrating macrophages are typically classified as M2, although some classify them as myeloid-derived suppressor cells (MDSC).


What's The Difference Between M1 and M2 Macrophages? Table


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  1. I would make one comment on your M1/M2 article. While M1 are known for tumoricial activity mostly due to NO- production (some of it is due to TNFa), thats only for mouse/rodent macrophage. Human macrophage stimulated the same way (typically IFNg and LPS) do not secrete appreciable NO- nor kill near as well as mouse macrophage. Many of those reports came out around 1993.

  2. Hi Ken, thanks for adding that in. I know you are a macrophage enthusiast so I appreciate you pointing out the differences between human and mouse macrophages.

  3. Would it be possible to perform immunofluorescence using arginase-1 and iNOS in mouse tissue samples in order to distinguish M1 and M2 subpopulations? or is it better to use cd80 and cd206?

  4. Hi Anne, does one or all of these M2 subs specifically switch to down regulate the helper T cells allowing myeloid cancer spread.

    • The tumor associated macrophages (TAM) are definitely involved in dampening the immune response to tumors but in general all of the M2 subsets described have features that would tend to down regulate T cells.

    • Hi Giri,
      I’ll take the second question first: PMA is a phorbol ester and will activate cells by turning on protein kinase C. For THP-1 cells it is used to make them more macrophage-like. I’m guessing they are M1 like in that situation but I haven’t used that model much so I don’t know for sure.

  5. Hi Anne my daughter and granddaughter both suffering with lymes disease and after much expense finding various doctors all over the Uk they have been advised taking M1 & M2 do you think this could help ? I’ll do appreciate your thoughts we are distraught and concerned as they have suffered since last July and unable to function. Work or attend kindergarten .. many thanks Gina

    • Hi Gina, sorry your daughter and granddaughter are having to cope with Lyme Disease. I am not a physician so I cannot give any advice on treatment. I have checked with the CDC and NIH resources and it seems that if a course of antibiotics does not resolve the problems it is difficult to know what to do. Consult with the best physicians you can find and hope for the best is all I can recommend. I wish you and your family the best of outcomes.

    • Polarization is affected by the extracellular signals received the macrophage. Cytokines, chemokines and pathogens all contribute signals that are then integrated into a phenotype.

    • I don’t have a good answer to that one. I would refer you to the literature. There may be a protein marker but I am not aware of one.

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  7. Hi, everyone talked about M1 and M2. Does another form M0 exist? Is there a way to revert back from form polarized form to M0 or the other.

    • Yes, there have been descriptions of M0 but I’m not recalling how these are distinguished. And cells can switch from M2 to M1 or vice versa. It is not a fixed phenotype; I think of it as different activation profiles depending on the microenvironment.

  8. Hello Ms. Anne Lodge,
    Recently I stained macrophages with F4/80, CD206 and iNOS . I found a large proportion of F4/80 macrophages are double positive with the expression of both CD206 and iNos. Is it possible for macrophages to express both M1 and M2 markers on the same macrophage? If so what is the function of these cells?

    • Interesting! I suppose these were mouse macrophages, right? Clearly it’s possible for macrophages to express both M1 and M2 markers since you’ve just caught them doing it. I think it is important to remember that some distinctions are not black and white but more of a spectrum and that is true of the M1 vs M2 as well as many T cells that aren’t exclusively TH1 or TH2. I would be interested in the cytokine/chemokine output of your macrophages.

  9. Hi, everyone! I have a doubt and would like to ask. My macrophages (Raw 264.7) have been induced to M2 state with IL-4. I don’t know if the cells will switch to M0 after changing to a medium without IL-4. Are macrophages induced to M2 still M2 after passage?

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