Calprotectin: the pathway in the body

This page shows the biochemical pathway behind the laboratory value Calprotectin (stool): which stations follow one another, which enzymes carry out each step and which cofactors they use. Every statement has a source. The page describes general textbook knowledge and says nothing about any individual person.

In brief

Calprotectin is a protein made of two subunits, S100A8 and S100A9. It is abundant in neutrophil granulocytes and binds metal ions such as zinc and manganese outside the cell.

The pathway step by step

1. Neutrophils → Calprotectin in cytosol · Calcium Inside these cells, calprotectin is present in large amounts. It consists of the proteins S100A8 and S100A9, which pair up; calcium stabilises the pair. Source 1, 2
2. Calprotectin in cytosol → Migration into tissue · Signalling molecules Signalling molecules from the tissue make neutrophils stick to the vessel wall. They squeeze between the cells and migrate to the site of inflammation, for example into the gut wall. Source 4
3. Migration into tissue → Release On strong activation and when the cell breaks down, calprotectin reaches the outside. The DNA nets that neutrophils cast out also carry it with them. Source 1, 4
4. Release → In the gut contents Once calprotectin reaches the gut, it persists there for some time because digestive enzymes break it down only slowly. This is why it can be measured in stool. Source 1
5. Calprotectin outside → Zinc and manganese held · Calcium Between the two subunits lie two binding sites. They grip zinc and manganese very tightly; iron and nickel are bound there too. Calcium makes the binding tighter. Source 2
6. Zinc and manganese held → Metals withheld Bacteria and fungi need zinc and manganese for their own enzymes. When the ions are bound, less of them is available to these microbes. This principle is called nutritional immunity. Source 2
7. Calprotectin outside → Signal to immune cells Calprotectin attaches to the receptors TLR4 and RAGE. The cell reads this as a sign of damaged tissue and then forms further signalling molecules. Source 3, 1

Cofactors in this pathway

• Calcium — Holds the two subunits together and tightens the binding of zinc and manganese Source 1, 2In the ORY catalogue as a laboratory value: Calcium (intrazellulär)
• Zinc — Bound very tightly at the two metal pockets between the subunits Source 2In the ORY catalogue as a laboratory value: Zink
• Manganese — Occupies the second metal pocket of calprotectin together with zinc Source 2
• Iron — Bound at the same metal pocket as manganese Source 2In the ORY catalogue as a laboratory value: Eisen
• Nickel — Also binds at the pocket between S100A8 and S100A9 Source 2

Sources

1. Jukic A, Bakiri L, Wagner EF et al. Calprotectin: from biomarker to biological function. Gut 2021 · PubMed 34145045
2. Zygiel EM, Nolan EM. Transition Metal Sequestration by the Host-Defense Protein Calprotectin. Annu Rev Biochem 2018 · PubMed 29925260
3. Vogl T, Tenbrock K, Ludwig S et al. Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock. Nat Med 2007 · PubMed 17767165
4. Kolaczkowska E, Kubes P. Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol 2013 · PubMed 23435331

Related pathways

• Candida — neutrophils
• Histamine — release
• Vitamin D — Calcium (intrazellulär), Zink
• 8-OHdG — Zink, Eisen
• Borrelia — Zink, Eisen

As of 2026-09-16. Draft, written by Claude to schema v2; sources checked in PubMed; expert approval pending
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