S100A8A9

S100A8A9 refers to the calprotectin complex formed by the two S100 family proteins, S100A8 and S100A9. These calcium-binding proteins are highly expressed in myeloid cells, especially neutrophils and to a lesser extent monocytes, and are released during activation or cell death. The term S100A8A9 is commonly used to denote the heterodimer rather than a single gene product.

The S100A8 and S100A9 genes lie in a cluster on chromosome 1q21 and are often co-expressed during myeloid differentiation. In resting cells, the two proteins reside in the cytosol as a heterodimer and can be secreted in response to inflammatory stimuli. Upon binding calcium, they form the calprotectin complex, which can further assemble into higher-order structures under certain conditions.

Calprotectin has multiple roles in the immune response. It participates in antimicrobial defense by sequestering essential transition metals such as zinc and manganese, limiting nutrient availability to pathogens. It also functions as a damage-associated molecular pattern (DAMP), engaging receptors such as TLR4 and RAGE to amplify inflammatory signaling and recruit leukocytes. This dual activity links calprotectin to both antimicrobial defense and inflammatory regulation.

Clinically, calprotectin is a widely used biomarker of inflammation. Fecal calprotectin is a noninvasive indicator of intestinal inflammation and is commonly used in inflammatory bowel disease management. Elevated levels can also be observed in systemic infections, autoimmune diseases, and other conditions associated with neutrophil activation. The S100A8A9 complex is frequently referred to in literature as calprotectin or as the MRP8/14 heterodimer.