Calprotectin: from biomarker to biological function

Abstract

The incidence of inflammatory bowel diseases (IBD) emerged with Westernisation of dietary habits worldwide. Crohn’s disease and ulcerative colitis are chronic debilitating conditions that afflict individuals with substantial morbidity and challenge healthcare systems across the globe. Since identification and characterisation of calprotectin (CP) in the 1980s, faecal CP emerged as significantly validated, non-invasive biomarker that allows evaluation of gut inflammation. Faecal CP discriminates between inflammatory and non-inflammatory diseases of the gut and portraits the disease course of human IBD. Recent studies revealed insights into biological functions of the CP subunits S100A8 and S100A9 during orchestration of an inflammatory response at mucosal surfaces across organ systems. In this review, we summarise longitudinal evidence for the evolution of CP from biomarker to rheostat of mucosal inflammation and suggest an algorithm for the interpretation of faecal CP in daily clinical practice. We propose that mechanistic insights into the biological function of CP in the gut and beyond may facilitate interpretation of current assays and guide patient-tailored medical therapy in IBD, a concept warranting controlled clinical trials.

Protein Cargo of Salivary Small Extracellular Vesicles as Potential Functional Signature of Oral Squamous Cell Carcinoma

“…Finally, the CLUSTER S/SEV OSCC_LNM was specifically associated to GO groups related to activities against pathogen agents, such as "metal sequestration by antimicrobial proteins" (associated to LCN2, LTF, S100A9-see Table 6 for the FC in S/SEV OSCC_LNM); "growth of symbiont in host" (associated to ELANE, MPO, PGLYRP1-see Table 6 for the FC in S/SEV OSCC_LNM); and "antimicrobial peptides" (associated to ELANE, GAPDH, LCN2, LTF, MPO, PGLYRP1, PI3, PRTN3, RNASE3, S100A12, S100A9-see Table 6 for the FC in S/SEV OSCC_LNM). Proteins of these groups, such as lactoferrin (LFT,), lipocalin-2 (LCN2), S100A9 (forming with S100A8 the heterodimeric complex calprotectin), neutrophil elastase (ELANE), peptidoglycan recognition protein 1 (PGLYRP1), and myeloperoxidase (MPO), are widely described for their antibacterial activity or for their role as inflammatory markers [44][45][46][47][48]. The enrichment of these proteins in the S/SEVs from patients with OSCC_LNM could be indicative of dysbiotic signatures occurring during tumor progression.…”

The Role of E3 Ubiquitin Ligases and Deubiquitinases in Inflammatory Bowel Disease: Friend or Foe?

“…Ring finger protein 5 (RNF5) expression was found to be decreased in the colonic inflammatory mucosa of IBD patients, and was negatively associated with S100 calcium binding protein A8 (S100A8) expression ( 99 ). S100A8 can induce neutrophils chemotaxis as well as promoting the expression of pro-inflammatory cytokines in immune cells ( 168 ). The inverse correlation of RNF5/S100A8 was consistent with the clinical severity of IBD patients, suggesting that the RNF5/S100A8 axis may play a role in the development of IBD ( 99 ).…”

Prognostic value of circulating calprotectin levels on the clinical course of COVID-19 differs between serum, heparin, EDTA and citrate sample types

“…Calprotectin (CLP) is a heterodimeric complex formed by two calcium-binding proteins S100A8 and S100A9, also known as myeloid-related protein (MRP)-8 and MRP-14. CLP is typically expressed and secreted by neutrophils, monocytes, and activated macrophages but can also be expressed and secreted by other cell lines including but not limited to dendritic cells, endothelial cells, keratinocytes and squamous mucosal epithelium [3] . CLP is part of the innate immune response and contributes to the inflammatory process through the recruitment of leucocytes, binding of arachidonic acid, and the expression of pro-inflammatory and anti-inflammatory mediators.…”

“…CLP acts as an endogenous ligand of Toll-like receptor 4 (TLR4) and receptor for advanced glycation endproducts (RAGE) [4] . Furthermore, CLP has an antimicrobial activity and plays a role in cell proliferation, differentiation and apoptosis [3] .…”