In this section we will look into what role calprotectin play in neutrophil activation.
Calprotectin is a S100 protein
Calprotectin is a heterodimer of two calcium-binding proteins and belongs to the S100 protein family (Synonyms: S100A8/A9 or MRP8/14). It is released from activated and consumed immunocytes, such as neutrophils, monocytes and macrophages1-5 during inflammation and upon bacterial infection. Calprotectin is well known extracellular alarmin or damage associated molecular pattern (DAMP) protein. It exerts its pro-inflammatory activity via receptors such as RAGE and TLR4, and NF-kB and p38 activation1,3,5.
Calprotectin also has anti-microbial activity by the binding of zinc and manganese, which leads to so-called nutritional immunity by ‘’starving’’ the bacteria1,5,6.
What is NET (neutrophil extracellular traps)?
Neutrophils are the dominant leukocytes circulating the blood, and they are the first innate immune cells that are recruited to a site of infection. Here the neutrophils have several defence strategies, including the production of toxic reactive oxygen species (ROS), the release of anti-microbial factors and the formation of neutrophil extracellular traps (NET).
The NETs are composed of a mesh-like structure which consists of DNA strands, histones and antimicrobial proteins. They can therefore ensnare the microbes by localising and trapping pathogens within the sticky meshwork of chromatin, and also expose them to the highly concentrated anti-microbial factors6.
Calprotectin is one of most abundant proteins in the cytosol of neutrophils making up around 40 %-60% of the cytosolic proteins. Calprotectin is released from the neutrophils during inflammation, executing its pro-inflammatory function as alarmin, and is part of the anti-microbial factors in the NETs1,6,7. Both the calprotectin release and the neutrophil activation are regulated in negative-feedback loops. However, uncontrolled expression of calprotectin will also accelerate the neutrophil activation and trigger release of further pro-inflammatory factors leading, to inflammatory damage and septic shock1.
Neutrophils and calprotectin:
Neutrophils are major players in first-line defence against infection
Calprotectin is released from neutrophils and acts as anti-microbial factor and pro-inflammatory alarmin
Calprotectin is upregulated in infections and inflammatory conditions and a promising biomarker for neutrophil activation and inflammation
Calprotectin correlates with disease activity in multiple inflammatory conditions, both in infectious and non-infectious inflammatory conditions
Calprotectin – the promising early biomarker of neutrophil activation
Since calprotectin is released by activated neutrophils in inflammation in several infectious and non-infectious conditions, calprotectin is a promising biomarker for neutrophil activation and inflammatory conditions where it also correlates well with disease activity, including bacterial infections, sepsis and autoimmune inflammatory conditions, like rheumatic arthritis1-4.