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Introduction[edit | edit source]

Macrophage sheet.jpeg

Macrophages are specialised cells involved in the detection, phagocytosis and destruction of bacteria and other harmful organisms.[1] They are a diverse phenotype of professional phagocytic cells derived from bone-marrow precursors and parent monocytes in the peripheral blood.

  • Macrophages are essential for the maintenance and defence of host tissues, doing so by sensing and engulfing particulate matter and, when necessary, initiating a pro-inflammatory response. They migrate to and circulate within almost every tissue, patrolling for pathogens or eliminating dead cells.
  • Playing such a vast number of roles in both health and disease, the activation phenotype of macrophages can vary greatly ( substantial heterogeneity) and is largely dependent on the surrounding microenvironment - reflecting the required level of specialisation within the environment of any given tissue. This heterogeneity is reflected in their morphology, the type of pathogens they can recognise, as well as the levels of inflammatory cytokines they produce.
  • Macrophages also produce reactive oxygen species, such as nitric oxide, that can kill phagocytosed bacteria.

Location and Function of Macrophages[edit | edit source]

Below describes the location and function of a few different macrophage populations.

  1. Alveolar macrophage: Lung alveoli - Phagocytosis of small particles, dead cells or bacteria. Initiation and control of immunity to respiratory pathogens. The first line of defense against invading respiratory pathogens. They reside in pulmonary alveoli and the inter-alveolar septum in close proximity with pneumocytes.
  2. Histiocytes: Connective Tissue - Motile, phagocytic cells found in the loose connective tissue throughout the body, help the body heal after an injury or infection by removing dead cells, blood, micro-organisms (such as bacteria and fungus), and foreign material from the body.[2]
  3. Osteoclasts: Bone - Mediators of the continuous destruction of bone
  4. Interstitial macrophage (IM): gut - represent the largest pool of tissue macrophages in the body. [3]Recent evidence supports the notion that IMs perform important immune functions in the lung, notably in terms of innate immunoregulation[4].
  5. Kupffer cells: Liver- Initiate immune responses and hepatic tissue remodelling. Kupffer cells are the most abundant tissue macrophages as they constitute 80-90% of them.
  6. Microglia: Central nervous system - Elimination of old or dead neurons and control of immunity in the brain.
  7. Splenic macrophages (marginal zone, metallophilic and red pulp macrophages): Spleen marginal zone, red and white pulp - Elimination of dysfunctional or old red blood cells[1].

Homeostasis[edit | edit source]

Macrophages play a pivotal role in the maintenance of tissue homeostasis and in tissue regeneration after injury.

  1. Homeostasis eg In humans the tissue cellular turnover rate has been estimated to be more or less 1 million cells per second each day: the removal of apoptotic cells is constantly provided mainly by macrophages that reside in tissues, through an immunologically silent process known as efferocytosis. One of the hallmarks of this process is represented by the release of anti-inflammatory cytokines that prevent the development of inflammation. Defects in the clearance of apoptotic cells are directly linked to the development of inflammation and autoimmune diseases.
  2. Tissue Regeneration eg When an inflammatory process is triggered by the perturbation of tissue homeostasis, bone-marrow derived monocytes that circulate in the blood-stream are attracted to the site of inflammation. At the site of inflammation, monocytes differentiate into macrophages, which cooperate with resident cells for sustaining immunity or promoting resolution of inflammation and tissue regeneration.[5]

Role in Pathological Processes[edit | edit source]

It is becoming increasingly accepted that macrophages play a crucial role in many diseases associated with chronic inflammation, including atherosclerosis, obesity, diabetes, cancer, skin diseases, and even neurodegenerative diseases. It is therefore not surprising that macrophages in human diseases have gained significant interest during the last years[6]. Examples are given below.

  • Macrophage activation syndrome is caused by the effects of massive macrophage activation as seen in eg Systemic SARS-CoV-2-associated complications (acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation syndrome, edema, and pneumonia). [7]
  • Atherosclerosis is a chronic disease starting with the entry of monocytes into the subendothelium and the subsequent differentiation into macrophages. Macrophages are the major immune cells in atherosclerotic plaques and are involved in the dynamic progression of atherosclerotic plaques. Accumulating evidence has demonstrated that resident macrophages can proliferate under microenvironment stimuli and dominate plaque macrophage accumulation in all stages of atherosclerosis.[8]
  • Hepatic macrophage populations include different types of cells with plastic properties that can differentiate into diverse phenotypes to modulate their properties in response to different stimuli. They often regulate the activity of other cells and play an important role in many hepatic diseases. In response to those pathological situations, they are activated, releasing cytokines and chemokines; they may attract circulating monocytes and exert functions that can aggravate the symptoms.[9]
  • Adenoviruses, HIV, and the bacteria that cause tuberculosis are examples of microbes that cause disease by infecting macrophages.
  • Macrophages in fat tissue can cause inflammation which induces adipose cells to become resistant to insulin. This can lead to the development of diabetes.
  • Chronic inflammation caused by macrophages can also contribute to the development and growth of cancer cells.[10]

References[edit | edit source]

  1. 1.0 1.1 Immunology Macrophages Available from: (accessed 13.5.2021)
  2. Science keys Connective Tissue | Anatomy and Physiology Available from: (accessed 13.5.2021)
  3. Smith PD, Smythies LE, Shen R, Greenwell-Wild T, Gliozzi M, Wahl SM. Intestinal macrophages and response to microbial encroachment. Mucosal immunology. 2011 Jan;4(1):31-42. Available from: (accessed 13.5.2021)
  4. Liegeois M, Legrand C, Desmet CJ, Marichal T, Bureau F. The interstitial macrophage: A long-neglected piece in the puzzle of lung immunity. Cell Immunol. 2018 Aug;330:91-96. doi: 10.1016/j.cellimm.2018.02.001. Epub 2018 Feb 8. PMID: 29458975.Available from: 13.5.2021)
  5. Viola A, Munari F, Sánchez-Rodríguez R, Scolaro T, Castegna A. The metabolic signature of macrophage responses. Frontiers in immunology. 2019 Jul 3;10:1462.Available from: (accessed 13.5.2021)
  6. Schultze JL, Schmieder A, Goerdt S. Macrophage activation in human diseases. InSeminars in immunology 2015 Aug 1 (Vol. 27, No. 4, pp. 249-256). Academic Press.Available: 13.5.2021)
  7. Kosyreva A, Dzhalilova D, Lokhonina A, Vishnyakova P, Fatkhudinov T. The Role of Macrophages in the Pathogenesis of SARS-CoV-2-Associated Acute Respiratory Distress Syndrome. Frontiers in Immunology. 2021 May 10;12:1667.Available from: (accessed 13.5.2021)
  8. Lin P, Ji HH, Li YJ, Guo S. Macrophage plasticity and atherosclerosis therapy. Frontiers in Molecular Biosciences. 2021;8:324.Available from: (accessed 13.5.2021)
  9. Colino CI, Lanao JM, Gutierrez-Millan C. Targeting of hepatic macrophages by therapeutic nanoparticles. Frontiers in immunology. 2020;11.Available from: (accessed 13.5.2021)
  10. Thought co. Macrophages Available: (accessed 13.5.2021)