Macrophages

Abstract

Macrophages are an important component of the innate and adaptive immune system. Their ability to recognize, phagocytose and kill microbial pathogens is complemented by the production of a broad spectrum of pro‐ and anti‐inflammatory cytokines.

Keywords: macrophages; phagocytosis; receptors; cytokines; reactive oxygen intermediates; reactive nitrogen intermediates

Figure 1.

Relationship of monocytes, macrophages and myeloid DC. Common myeloid progenitor cells (CMPs) (derived from CD34+ haematopoietic stem cells) give rise to granulocyte–monocyte precursors and subsequently to monocytes. In the presence of M‐CSF monocytes will develop into macrophages. In contrast, exposure of monocytes to GM‐CSF plus IL‐4 or transendothelial migration of monocytes after phagocytosis leads to the generation of immature myeloid dendritic cells. As an alternative pathway, immature dendritic cells can also be generated from CMPs in the presence of GM‐CSF plus TNF. Upon contact with pathogens (e.g. LPS), certain cytokines (e.g. TNF‐α, IL‐1) or T cells (CD40L) immature dendritic cells acquire a mature phenotype (characterized by high levels of surface MHC class II antigens and costimulatory molecules (CD80 and CD86), IL‐12 p70 production and a strong T‐cell‐stimulatory capacity). When treated with M‐CSF, immature myeloid DCs turn into macrophages. Note that this is a simplified scheme, which does not depict all subpopulations and lineages of DCs. For details see Banchereau and Steinman and Ardavin .

Figure 2.

Synthesis of ROI and RNI by phagocytes. Professional phagocytes (macrophages or neutrophils) generate ROI and RNI by the myeloperoxidase (MPO), the inducible (or type 2) NO synthase (iNOS or NOS2) and the NADPH oxidase. There are several known interactions between these antimicrobial effector pathways, including (a) the consumption of peroxide (H2O2), generated from superoxide ( ) by the action of superoxide dismutase, in the MPO pathway; (b) the utilization of NOS2‐derived nitrite ( ) in the MPO pathway, leading to the production of nitryl chloride (NO2Cl) and nitrogen dioxide (.NO2) and (c) the generation of peroxynitrite (ONOO) from nitric oxide (.NO) and superoxide ( ).

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Further Reading

Brown GD (2006) Dectin‐1: a signalling non‐TLR pattern recognition receptor. Nature Reviews Immunology 6: 33–43.

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Strober W, Murray PJ, Kitani A and Watanabe T (2006) Signalling pathways and molecular interactions of NOD1 and NOD2. Nature Reviews Immunology 6: 9–20.

Williamson P and Schlegel RA (2004) Hide and seek: the secret identity of the phosphatidylserine receptor. Journal of Biology 3: 14.11–14.14.

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Bogdan, Christian(Apr 2006) Macrophages. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0004007]