Macrophages are very important members of the mononuclear phagocytic system. This notoriously heterogeneous system is composed of macrophages themselves in addition to dendritic cells, monocytes and their lineage committed progenitors. Although there is a lot of overlap between these cells types, regarding both cell surface markers and function, there are still some distinct features that can uniquely identify them.

Nowadays, it is almost impossible to talk about macrophages without mentioning dendritic cells, and vice versa. However, the most important and most widely accepted difference between these two types of cells is their capacity to stimulate naïve T cells. When it comes to their antigen presentation capacity, dendritic cells are superior. However, macrophages are heavily involved in a number of other metabolic functions, such as pathogen killing and wound and tissue repair, where dendritic cells are less prominent.

Macrophage development is strongly related to that of monocytes and dendritic cells, as part of the mononuclear phagocyte system. In general, macrophages develop from monocytes in the bone marrow, but they can also replenish themselves in peripheral tissues directly from local precursors.

 

CSF1 RANKL GM-CSF IFN-g TNF-a CD86 IFN-gR IL-12 CXCL9 CXCL10 IL-4 IL-13 Cd163 CD206 Il-4R CCL17 CCL22 CCL24 Arg1 MHC II CSF1 CSF1 CSF1 CSF1

 

HSC: Hematopoietic stem cell CFU-M: Colony forming unit-macrophage TNF-α: Tumor necrosis factor alpha IFN-γ: Interferon gamma RNS: Reactive nitrogen species
CFU-GM: Colony forming unit-granulocyte/macrophage Arg1: Arginase-1 enzyme CXCL and CCL: Chemokines SR: Scavenger Receptors ROS: Reactive oxygen species
IL-: Interleukin- CSF1: Macrophage colony-stimulating factor 1 (M-CSF) RANKL: Receptor activator of NF-κB ligand GM-CSF: Granulocyte macrophage-colony stimulating factor  

 

The injury: macrophages are recruited and differentiated in response to an injury. An injury is not just a physical or traumatic damage, but also infectious, toxic, ischemic, autoimmune and other types of insults. This wound evolves depending on many factors, and macrophages have an essential role in eliminating the damage and repairing the tissue. However, a delicate balance of all the factors involved dictates if an injury is effectively controlled or if it escalates and evolves into a chronic or fatal event. To complicate the picture even further, there are several types of macrophages, which can be linked to specific functions. Although several macrophage subpopulations will be involved at any given time in the resolution of an injury, it seems that a predominant type can be associated with a particular stage of the injury.

 

Progression or severity of the condition

The characterization of different macrophages subtypes is complex and markers provided here should be used as a guideline. In general, a multiparameter approach will provide the best characterization. This includes expression of cell surface markers, profile of transcription factors, production of cytokines and induction of specific enzymes related to function. For a deeper understanding of macrophage biology and subtypes, we recommend further literature reading:

 

  1. Pollard, JW. 2009. Nat Rev Immunol. 9:259-70. (Development) PubMed
  2. Gliem, M. et al. 2009. Stroke. 43: 3352-7. (Macrophages and bleeding) PubMed
  3. Lech, M. et al. 2012. Mediators Inflamm. 2012:951390 (Macrophages subsets and function) PubMed
  4. Biswas, SK. and Mantovani, A. 2010. Nat Immunol. 2010. 11:889-96. (Macrophages subsets and function) PubMed
  5. Hao, NB. et al. 2012. Clin Dev Immunol. 2012:948098 (TAM) PubMed

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