MRP8/ MRP14

S100A8 and S100A9 (also known as MRP8 and MRP14, respectively) are Ca2+-binding proteins belonging to the S100 family. MRP8/14 are identical to the cystic fibrosis antigen. They are frequently found in the form of heterodimers, while homodimers are very rarely detected due to their stability (Wang S et al. 2018). The MRP8/14 dimer is constitutively expressed in neutrophils and monocytes as a Ca2+ sensor and is involved in cytoskeletal restructuring and arachidonic acid metabolism.

During inflammation, MRP8/14 is actively released and plays a critical role in modulating the inflammatory response by stimulating leukocyte recruitment and cytokine secretion.

MRP8/14 proteins are expressed during myeloid differentiation, are abundant in granulocytes and monocytes, and form a heterodimeric complex in a Ca2+-dependent manner. Phagocytes expressing MRP8 and MRP14 are among the early infiltrating cells and dominate acute inflammatory lesions.

Elevated serum levels of MRP8/14 were found in patients with a number of inflammatory diseases such as cystic fibrosis, rheumatoid arthritis, and chronic bronchitis, suggesting a conceivable extracellular role for these proteins. In patients with juvenile rheumatoid arthritis (JRA), MRP8 and MRP14 were strongly expressed in infiltrating neutrophils and monocytes in inflamed joints and could also be measured in synovial fluid at significantly higher concentrations. The concentrations of MRP8/MRP14 in serum correlated well with those in synovial fluid (r = 0.78) and showed a strong correlation with disease activity. Soluble MRP8/14 complexes may exert various functions, e.g., inhibition of casein kinases, binding to cytoskeletal proteins, antimicrobial activity. MRP8 and MRP14 thus represent two molecular parameters for the early events of inflammatory responses, revealing interesting aspects for the pathomechanism of chronic inflammatory responses.

MRP8/14 is a potential biomarker for diagnosis and follow-up as well as a predictive indicator for therapeutic responses to inflammation-related diseases (Frosch M et al.2000).

It is possible that MRP8 and MRP14 play an important role in leukocyte trafficking.

Since blockade of MRP8/14 activity by small molecule inhibitors or antibodies ameliorates pathological conditions in mouse models, the heterodimer may have potential as a therapeutic target.

1. Frosch M et al.(2000) Myeloid-related proteins 8 and 14 are specifically secreted during interaction of phagocytes and activated endothelium and are useful markers for monitoring disease activity in pauciarticular-onset juvenile rheumatoid arthritis. Arthritis Rheum 43:628-637.
2. Kerkhoff C et al (1998) Novel insights into structure and function of MRP8 (S100A8) and MRP14 (S100A9). Biochim Biophys Acta 1448:200-211.
3. Sorg C (1992). The calcium binding proteins MRP8 and MRP14 in acute and chronic inflammation. Behring Inst Mitt 91:126-37.
4. Wang S et al (2018) S100A8/A9 in inflammation. Front Immunol 9:1298.