Macrophages

For the most part, the body's macrophages are to be found in vulnerable locations and in places which are likely sites of infection. Here they can live for many months - and occasionally longer - ready to respond to any pathogen they come across. A small number act as "scavengers," being carried along by the blood, where they may encounter pathogens or damaged cells. Such macrophages have a half-life of only about a day.

Macrophages begin life as monocytes, which will mature, under certain influences, into macrophages or dendritic cells. Monocytes are produced by bone marrow and are released from there into the bloodstream. The majority of them migrate to the spleen - a kind of monocyte base - or vulnerable areas such as the lungs. Once in these areas they generally mature into macrophages, with each location engendering peculiar macrophages. This allows the body to maintain a regular turnover of macrophages in these areas.

There are actually two types of macrophages - M1 and M2. M2 is the phenotype of the majority of resident macrophages which remain in tissue. Here, they can respond to any pathogens which they may encounter - as well as damaged cells - and can initiate the immune response.

In the initial stages of inflammation, however, a lot of the "work" is done by neutrophils. After around 48 hours the initial "wave" of neutrophils will have aged and the neutrophils will have begun to die. The macrophages can then engulf them and clean up the general mess. This work is usually done by the resident macrophages. Macrophages will not tend be drawn to the site of infection in large numbers for some time. Usually, 24-28 hours is required before monocyte levels start to build up.

Macrophages are also heavily involved in tissue repair.  M2 "repair" macrophages are capable of producing molecules which aid in tissue repair, but their primary role is to rid the area of any damaged tissue. They also release cytokines which attract other cells which can help to the area and they produce factors which aid in angiogenesis. More generally, M2 macrophages additionally produce anti-inflammatories which regulate the immune response and keep it from harming the body.

Now, when pathogens or damaged cells are detected, the monocytes (and any macrophages which are in the bloodstream) are attracted to the area by inflammatory cytokines. They leave the blood flow and enter the interstitial fluid, where they then move by chemotaxis towards the infected area. Once there, the monocytes are stimulated to become macrophages (or dendritic cells) through numerous processes. In the case of substantial infection, large numbers of monocytes will travel to the site of infection, where they will mature into macrophages.

M1 "killer" macrophages are particularly oriented to hunting down pathogens and cellular debris and phagocytising them. It is possible for T cells - which will become very important to us soon - to cause M1 macrophages to become particularly aggressive. Indeed, macrophages have an incredible appetite and have been known to eat iron filings, for instance.

In general, macrophages are also effective antigen presenting cells and, as we have seen in some detail, are responsible for releasing many inflammatory cytokines and for mediating the immune response as a whole.

For those of you who are interested, the macrophage itself looks like this:

(a) A macrophage of a mouse involved in phagocytising two pathogens. (Image courtesy "magnaram" (via Wikipedia))

(b) A schematic representation of a macrophage. (Image courtesy "A. Rad" (via Wikipedia))

Figure 1.52: The macrophage