Question

I need help coming up with an introduction for my lab report. The topic is MACROPHAGE FUNCTIONS. Can you please cite the work

Answer 1

Function of a Macrophage

Phagocytosis

The macrophage accomplishes its ongoing cleanup task by engulfing unwanted particles and 'eating' them. As mentioned before, a macrophage is an amoeba-type cell. Imagine a jelly-like blob oozing along, surrounding its prey, and swallowing it. This is essentially how a macrophage works. But let's take a closer look at the actual process.

A macrophage uses a process called phagocytosis to destroy and get rid of unwanted particles in the body. Phagocytosis literally means 'eat cell.' The process works like this: as the macrophage engulfs the particle, a pocket called a phagosome is formed around it. Then, enzymes are released into the phagosome by an organelle within the macrophage called a lysosome. Much like the enzymes in our own stomach are released to digest our food, the enzymes released by the lysosome digest the particle. The remaining debris, or what is left of the particle, exits the macrophage to be absorbed back into the body.

Phagosome Phagocytosis Bacteria Phagolysosome Receptors Lysosome Exocytosis

Fig 1 : Phagocytosis

The neutrophils are at first attracted to a site, where they perform their function and die, before they are phagocytized by the macrophages. When at the site, the first wave of neutrophils, after the process of aging and after the first 48 hours, stimulate the appearance of the macrophages whereby these macrophages will then ingest the aged neutrophils.

The removal of dying cells 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 and 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. Typhoidal Salmonellae induce their own phagocytosis by host macrophages in vivo, and inhibit digestion by lysosomal action, thereby using macrophages for their own replication and causing macrophage apoptosis.Macrophages can digest more than 100 bacteria before they finally die due to their own digestive compounds.

Macrophages are versatile cells that play many roles.As scavengers, they rid the body of worn-out cells and other debris. Along with dendritic cells, they are foremost among the cells that present antigens, 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 and 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 (MHCII), 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. T cells that express the T cell receptor which recognizes the antigen-MHCII complex (with co-stimulatory factors- CD40 and CD40L) cause 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, producing chemical mediators known as lymphokines that stimulate macrophages into a more aggressive form.

Role in muscle regeneration

The first step to understanding the importance of macrophages in muscle repair, growth, and regeneration is that there are two "waves" of macrophages with the onset of damageable muscle use – subpopulations that do and do not directly have an influence on repairing muscle. The initial wave is a phagocytic population that comes along during periods of increased muscle use that are sufficient to cause muscle membrane lysis and membrane inflammation, which can enter and degrade the contents of injured muscle fibers.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.The second group is the non-phagocytic types that are distributed near regenerative fibers. These peak between two and four days and remain elevated for several days during the hopeful muscle rebuilding.The first subpopulation has no direct benefit to repairing muscle, while the second non-phagocytic group does.

It is thought that macrophages release soluble substances that influence the proliferation, differentiation, growth, repair, and regeneration of muscle, but at this time the factor that is produced to mediate these effects is unknown. It is known that macrophages' involvement in promoting tissue repair is not muscle specific; they accumulate in numerous tissues during the healing process phase following injury.

Role in wound healing

Macrophages are essential for wound healing.They replace polymorphonuclear neutrophils as the predominant cells in the wound by day two after injury.Attracted to the wound site by growth factors released by platelets and other cells, monocytes from the bloodstream enter the area through blood vessel walls.Numbers of monocytes in the wound peak one to one and a half days after the injury occurs. Once they are in the wound site, monocytes mature into macrophages. The spleen contains half the body's monocytes in reserve ready to be deployed to injured tissue.

The macrophage's main role is to phagocytize bacteria and damaged tissue,and they also debride damaged tissue by releasing proteases.Macrophages also secrete a number of factors such as growth factors and other cytokines, especially during the third and fourth post-wound days. These factors attract cells involved in the proliferation stage of healing to the area.Macrophages may also restrain the contraction phase.Macrophages are stimulated by the low oxygen content of their surroundings to produce factors that induce and speed angiogenesis and they also stimulate cells that re-epithelialize the wound, create granulation tissue, and lay down a new extracellular matrix. By secreting these factors, macrophages contribute to pushing the wound healing process into the next phase.

Role in limb regeneration
Scientists have elucidated that as well as eating up material debris, macrophages are involved in the typical limb regeneration in the salamander.They found that removing the macrophages from a salamander resulted in failure of limb regeneration and a scarring response.

Role in iron homeostasis

Macrophages play a key role in removing dying or dead cells and cellular debris. Erythrocytes have a lifespan on average of 120 days and so are constantly being destroyed by macrophages in the spleen and liver. Macrophages will also engulf macromolecules, and so play a key role in the pharmacokinetics of parenteral irons.

The iron that is released from the haemoglobin is either stored internally in ferritin or is released into the circulation via ferroportin. In cases where systemic iron levels are raised, or where inflammation is present, raised levels of hepcidin act on macrophage ferroportin channels, leading to iron remaining within the macrophages.

Role in pigment retainment

Melanophages are a subset of tissue-resident macrophages able to absorb pigment, either native to the organism or exogenous , from extracellular space. In contrast to dendritic juncional melanocytes, which synthesize melanosomes and contain various stages of their development, the melanophages only accumulate phagocytosed melanin in lysosome-like phagosomes.This occurs repeatedly as the pigment from dead dermal macrophages is phagocytosed by their successors, preserving the tattoo in the same place.

Role in tissue homeostasis

Every tissue harbors its own specialized population of resident macrophages, which entertain reciprocal interconnections with the stroma and functional tissue.These resident macrophages are sessile , provide essential growth factors to support the physiological function of the tissue (e.g. macrophage-neuronal crosstalk in the guts),and can actively protect the tissue from inflammatory damage.