Dane Patterson
M2 Macrophage
Naturally an individual which is experiencing high levels of aggravating factors leading
to macrophage activation will develop tissue damage due to the immune effecter role that the
standard/classical macrophage plays. When an individual is exposed to continuous damage the
body naturally shifts to a repair stage to clean up after the damage of the standard/classical
macrophage. The destructive and reparative stages of a macrophage have been divided into M1
and M2 macrophage subtypes respectively.
M1 macrophage cells have an IL-12High, IL-
23High, IL-10Low phenotype and are associated with TH1 mediated immune responses. In
contrast M2 macrophages cells are marked by IL-12Low, IL-23Low, IL-10High and have an
ability to produce inflammatory cytokines gauged towards repair of tissues making them TH2
associated (Matovani, et al, 2005). It would follow that in an individual which has undergone a
systemic inflammatory disorder for extended periods would have a greater disposition to develop
high levels of M2 macrophage subtypes. Julie is one such individual; the presence of SLE
suggested by elevated levels of CRP would cause a polarization of the subtypes of macrophages
to the M2 subtype.
In a standard case a polarization towards the M2 macrophage subtype would be
appropriate after the initial inflammatory responses to clean up after the apoptotic affects of the
M1 macrophage subtype. The presence of M2 macrophage is marked by the inhibition and
activation of multiple components of the immune system. Through its repair role the M2 subtype
inhibits NK Cells, CD8+ T Cells, TH1 and promotes TH2, EGF expression for repair (J.Clin
Invest., 2007). The down regulation of NK cells, CD8+, and TH1 inhibits the immune system’s
ability to determine if a cell is operating normally. Rather than identifying self tissue and
destroying any abnormalities the M2 macrophage stimulates the growth of existing cells and
destroys any non-self components that are free from the cells in the environment. This has
multiple implications for the progression of Julie’s tumors and plays a role in allowing for the
metastasis of the cancer.
With the immune systems emphasis being shifted from detection of pathogens to repair
one could consider Julie to be in a highly immune compromised state. Cancer has many ways to
evade detection by ones immune system and if the individual is already experiencing an immune
augmenting disease there is an even greater likelihood that the cancer will be allowed to
progress. Additionally, the polarization towards M2 macrophage phenotypes induces many
growth factors to be released and encourages not just normal cells but also tumor cells to grow.
Dane Patterson
M2 Macrophage
The shift from TH1 to TH2 becomes an additional factor to the problem due to a de-emphasis of
detection of self tissue and rather identifying abnormal material around the cells. This gives the
existing immune surveillance components little to no way to detect that there is an abnormal cell
growth present.
In Julie’s case a possible beneficial process to her progressive case of cancerous growth
would be to establish a better balance between M1 and M2 macrophage phenotypes. While it is
necessary for one to have the ability to repair damaged tissue especially in Julie’s case with SLE
it is still necessary to maintain a system of self checking. It has been suggested from various
studies that IFN-γ can induce the expression of M1 macrophages where IL-4 and IL-13 inhibit
M1 and induce M2 macrophage formation (J.Clin Invest., 2007). This suggests that increased
levels of IFN-γ would shift the ratio of M2 back to M1. This would most likely need to be
administered locally in Julie’s case to allow for other locations where SLE has destroyed tissue
to be repaired uninhibited. Another problem is present that contributes to the amount of
stimulating EGF that a cancerous agent would be subject to in Julie’s case. The state of stress
and tissue damage not only leads to the polarization of macrophages to the M2 subtype but
increases the presence of Heat Shock Proteins (HSP’s) present in cells under stress.
Dane Patterson
M2 Macrophage
Works Cited
1. J. Clin. Invest.117:1137–1146 (2007). doi:10.1172/JCI31405.
2. Mantovani, A. Sica, A. Locati, M. Immunity. Vol. 23, October, 2005 Elsevir Inc DOI
10.1016/j.immuni.2005.10.001 pg 344-346