Relationship Between Fecal Calprotectin, Intestinal Inflammation, and Peripheral Blood Neutrophils in Patients with Active Ulcerative Colitis

Abstract

Active ulcerative colitis (UC) is associated with elevated granulocytes and monocytes/macrophages (GM) which show activation behavior and increased survival time. Further, fecal calprotectin (a stable neutrophil protein) level parallels intestinal inflammation and can predict UC relapse. Since GM are major sources of inflammatory cytokines and chemokines, they are suspected to have roles in the initiation and perpetuation of UC. Our objective was to investigated relationships between peripheral blood (PB) neutrophils, calprotectin, and UC disease activity. Full PB and calprotectin were determined in 69 healthy controls and 31 patients with UC, then 7 randomly selected patients received GM adsorptive apheresis (GMA) with Adacolumn, 10 sessions of 60-min duration each. Patients with UC had higher neutrophil counts (P < 0.001), but lower lymphocyte counts (P < 0.001) compared with controls. Further, fecal calprotectin levels showed a correlation with UC clinical activity index (CAI; P < 0.001) and mucosal inflammation (P < 0.001). Following GMA, there were falls in neutrophils (P < 0.02), CAI (P < 0.02) and calprotectin (P < 0.02). In conclusion, GM appear to contribute to intestinal inflammation and UC activity and reduction of these cells by GMA should benefit patients with active UC. Further, the correlations among calprotectin, UC activities, and PB neutrophils should serve as the basis for preemptive actions to control this disease.

Luminal Cathepsin G and Protease-Activated Receptor 4

“…16 Moreover, neutrophil accumulation within epithelial crypts and in the intestinal lumen directly correlates with clinical disease activity and epithelial injury. 17,18 We have described earlier that activity of MPO and elastase, two components of neutrophils, is markedly increased in fecal supernatants from patients with UC, in comparison with supernatants from healthy subjects. 11 However, even though Cat-G is one of the most abundant proteins found in human and mouse neutrophils, 19 no clinical studies have evaluated so far its involvement in the pathogenesis of IBD.…”

The Role of Gut Permeability and Serine-Proteases in the Pathomechanism of Irritable Bowel Syndrome and Inflammatory Bowel Diseases

“…It is also well-known that neutrophil transmigration across mucosal epithelium is a hallmark of inflammatory conditions, such as IBD 69 . Moreover, neutrophil accumulation within epithelial crypts and in the intestinal lumen directly correlates with clinical disease severity and epithelial injury 70,71 . Even though catepsin-G is one of the most abundant proteins found in human and mouse neutrophils 72 , no clinical studies have so far evaluated its involvement in the pathogenesis of IBD.…”

Visceral antinociceptive and proinflammatory effects of proteinase activated receptor-4 and its role in the pathogenesis of ulcerative

“…administration of Cat-G reversed the colorectal hypersensitivity in mice evoked by WAS, but not by TNBS, contrary to PAR-4-AP which was effective in both models. This finding can be explained by the non-specificity of Cat-G on PAR-4, that is, Cat-G may disarm PAR-1 and PAR-2 on human bronchial fibroblasts (41), and it induces apoptosis via a PAR-independent mechanism in cardiomyocytes (37). On the other hand, PAR expression may be influenced by inflammatory mediators released in certain conditions, therefore local PAR signalling may be altered (41,42).…”

“…(76). Neutrophil accumulation within epithelial crypts and in the intestinal lumen directly correlates with clinical disease activity and epithelial injury (23,41).…”

“…Moreover, granulocyte and monocyte/macrophage adsorptive apheresis reduced clinical activity index in UC patients (41). Neutrophils can release a large number of proteins from their major granule populations, primary (azurophilic) and secondary (specific) granules.…”