M1 and M2 Macrophages: Oracles of Health and Disease

Abstract

The purpose of immunology is simple. Cure or prevent disease. M1/M2 is useful because it is simple. M1/M2 describes the two major and opposing activities of macrophages. M1 activity inhibits cell proliferation and causes tissue damage while M2 activity promotes cell proliferation and tissue repair. Remarkably, the molecules primarily responsible for these "Fight" (NO) or "Fix" (Ornithine) activities both arise from arginine, and via enzymatic pathways (iNOS and arginase) that down regulate each other. The names M1 and M2 were chosen because M1 and M2 macrophages promote Th1 and Th2 responses, respectively. Products of Th1 and Th2 responses (e.g., IFN-γ, IL-4) also down regulate M2 and M1activity, respectively. Thus, M1/M2 demonstrated the importance of Innate Immunity and how it is linked to Adaptive Immunity in a beautifully counterbalanced system. "Civilization" and increased longevity present new disease challenges such as cancer and atherosclerosis that do not display classical "foreign" antigens. And, these diseases are often associated with (or caused by) M1- or M2- type responses that were formerly useful for fighting infections, but now are inappropriate in our increasingly "germ-free" societies. In turn, there is considerable potential for modulating M1 or M2 Innate responses in modern diseases to achieve better health. Finally, since M1 and Th1 (or M2 and Th2) often work in concert to produce characteristic immune responses and disease pathologies, it is recommended that Immune Type 1 or 2 (IT1, IT2) would be a simpler and unifying terminology going forward.

Structure–activity relationship of immunomodulating pectins from elderberries

“…Macrophages are formed through differentiation of monocytes, and take part in both innate and adaptive immunity [55]. Their role is to remove microorganisms during infections, in addition to interact with and stimulate lymphocytes.…”

“…Their role is to remove microorganisms during infections, in addition to interact with and stimulate lymphocytes. In addition, macrophages also play an important anti-inflammatory role and can decrease immune reactions through the release of cytokines [55]. Macrophages that encourage inflammation are called M1 macrophages, whereas those that decrease inflammation and encourage tissue repair are called M2 macrophages [55].…”

Hepatic CD206-positive macrophages express amphiregulin to promote the immunosuppressive activity of regulatory T cells in HBV infection

“…Our data showed at least 3 subsets of macrophages in HBV-infected livers, based on the expression of CD80 and CD206: CD206 + CD80 lo/+ , CD206 2 CD80 + , and CD206 2 CD80 2 . CD206 is the marker of anti-inflammatory M2-type macrophages [24,40]. Therefore, these CD206 + macrophages might be M2 macrophages.…”

Targeting Inflammation to Improve Tumor Drug Delivery

“…Indeed, this macrophage shift from pro-tumor M2 phenotype to anti-tumor M1 phenotype has been proposed as a beneficial anti-cancer therapeutic target [57,58]. Importantly, there is evidence indicating that COX-2 is an important participant in macrophage polarization [59].…”