Macrophage

What is a Macrophage?

Macrophages are white blood cells within tissues, produced by the division of monocytes. Human macrophages are about 21 micrometres in diameterin diameter. Monocytes and macrophages are phagocytes, acting in both non-specific defense (innate immunity) as well as to help initiate specific defense mechanisms (adaptive immunity) of vertebrate animals.

Their role is to phagocytose (engulf and then digest) cellular debris and pathogens either as stationary or as mobile cells, and to stimulate lymphocytes and other immune cells to respond to the pathogen.

They can be identified by specific expression of a number of proteins including CD14, CD11b, F4/80 (mice)/EMR1 (human), Lysozyme M, MAC-1/MAC-3 and CD68 by flow cytometry or immunohistochemical staining. They move by action of Amoeboid movement.

When a leukocyte enters damaged tissue through the endothelium of a blood vessel (a process known as the leukocyte extravasation), it undergoes a series of changes to become a macrophage. Monocytes are attracted to a damaged site by chemical substances through chemotaxis, triggered by a range of stimuli including damaged cells, pathogens and cytokines released by macrophages already at the site. At some sites such as the testis, macrophages have been shown to populate the organ through proliferation.

Unlike short-lived neutrophils, macrophages survive longer in the body up to a maximum of several months.

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Macrophage Function

Phagocytosis

One important role of the macrophage is the removal of necrotic cellular debris in the lungs. Removing dead cell material is important in chronic inflammation, as the early stages of inflammation are dominated by neutrophil granulocytes, which are ingested by macrophages if they come of age.

The removal of necrotic tissue is, to a greater extent, handled by ''fixed macrophages'', which will stay at strategic locations such as the lungs, liver, neural tissue, bone, spleen and connective tissue, ingesting foreign materials such as pathogens, recruiting additional macrophages if needed.

When a macrophage ingests a pathogen, the pathogen becomes trapped in a phagosome, which then fuses with a lysosome. Within the phagolysosome, enzymes and toxic peroxides digest the pathogen. However, some bacteria, such as ''Mycobacterium tuberculosis'', have become resistant to these methods of digestion. Macrophages can digest more than 100 bacteria before they finally die due to their own digestive compounds.

Role in adaptive immunity

Macrophages are versatile cells that play many roles. As scavengers, they rid the body of worn-out cells and other debris. They are foremost among the cells that "present" antigen, a crucial role in initiating an immune response. As secretory cells, monocytes and macrophages are vital to the regulation of immune responses and the development of inflammation; they produce a wide array of powerful chemical substances (monokines) including enzymes, complement proteins, and regulatory factors such as interleukin-1. At the same time, they carry receptors for lymphokines that allow them to be "activated" into single-minded pursuit of microbes and tumour cells.

After digesting a pathogen, a macrophage will present the antigen (a molecule, most often a protein found on the surface of the pathogen, used by the immune system for identification) of the pathogen to the corresponding helper T cell. The presentation is done by integrating it into the cell membrane and displaying it attached to an MHC class II molecule, indicating to other white blood cells that the macrophage is not a pathogen, despite having antigens on its surface.

Eventually, the antigen presentation results in the production of antibodies that attach to the antigens of pathogens, making them easier for macrophages to adhere to with their cell membrane and phagocytose. In some cases, pathogens are very resistant to adhesion by the macrophages.

The antigen presentation on the surface of infected macrophages (in the context of MHC class II) in a lymph node stimulates TH1 (type 1 helper T cells) to proliferate (mainly due to IL-12 secretion from the macrophage). When a B-cell in the lymph node recognizes the same unprocessed surface antigen on the bacterium with its surface bound antibody, the antigen is endocytosed and processed. The processed antigen is then presented in MHCII on the surface of the B-cell. TH1 receptor that has proliferated recognizes the antigen-MHCII complex (with co-stimulatory factors- CD40 and CD40L) and causes the B-cell to produce antibodies that help opsonisation of the antigen so that the bacteria can be better cleared by phagocytes.

Macrophages provide yet another line of defense against tumor cells and somatic cells infected with fungus or parasites. Once a T cell has recognized its particular antigen on the surface of an aberrant cell, the T cell becomes an activated effector cell, chemical mediators known as lymphokines that stimulate macrophages into a more aggressive form. These activated macrophages can then engulf and digest affected cells much more readily. The macrophage does not generate a response specific for an antigen, but attacks the cells present in the local area in which it was activated.,,. These early-invading, phagocytic macrophages reach their highest concentration about 24 hours following the onset of some form of muscle cell injury or reloading. Their concentration rapidly declines after 48 hours.

A study conducted in 2006 showcased macrophage influences on muscle repair of soleus muscle on mice.

The first procedural step was to make sure macrophages are present in the muscle after onset of muscle injury, and then decrease their presence to see what effects were had on the muscle. By using anti-F4/80 to bind to macrophages and render them useless, it was seen that when the second wave of macrophages were depleted, there were many more lesions in the muscle cell membrane between the second and fourth day – showing muscle damage when repairing is suppose to occur. After testing for membrane lesions in both the total amount of muscle fibers present, it was noticed that most of the damage occurred in muscle cells that did not have the second subpopulation of macrophages present. Macrophages depletion prevents muscle membrane repair.

When examining muscle regeneration, there was a significant reduction in the amount of myonuclei. Depletion of macrophages caused, between the second and fourth day of repair, much less muscle regeneration compared to muscle with macrophage population.

Macrophages also play a role in Human Immunodeficiency Virus (HIV) infection. Like T cells, macrophages can be infected with HIV, and even become a reservoir of ongoing virus replication throughout the body.

Macrophages are believed to help cancer cells proliferate as well. They are attracted to oxygen-starved (hypoxic) tumour cells and promote chronic inflammation. Inflammatory compounds such as Tumor necrosis factor (TNF) released by the macrophage activates the gene switch nuclear factor-kappa B. NF-kB then enters the nucleus of a tumour cell and turns on production of proteins that stop apoptosis and promote cell proliferation and inflammation.

This article is licensed under the Creative Commons Attribution-ShareAlike License. It uses material from the Wikipedia article on "Macrophage" All material adapted used from Wikipedia is available under the terms of the Creative Commons Attribution-ShareAlike License. Wikipedia® itself is a registered trademark of the Wikimedia Foundation, Inc.