Calprotectin as a marker of inflammation in cystic fibrosis.

Calprotectin is an abundant neutrophil cytosolic protein released during neutrophil activation or death. The use of plasma calprotectin concentration as a marker of pulmonary inflammation was tested in 31 children with cystic fibrosis, none of whom was acutely unwell or pyrexic. Twenty three were receiving antibiotics, 21 had positive sputum cultures, but none of the traditional tests clearly diagnosed ongoing infection. Plasma calprotectin was significantly higher in the cystic fibrosis group than in matched controls. Sixteen children with cystic fibrosis had values above the control range (320-1570 micrograms/l). Their chest radiograph Northern score, an index of accumulated pulmonary involvement, and their plasma copper, an index of acute phase response, both correlated with plasma calprotectin. Plasma gamma-glutamyltransferase also correlated weakly with plasma calprotectin: thus, hepatic pathology may be a confounding variable. However, the data still suggested that plasma calprotectin is a better index of inflammation than the traditional indices in general use.

Calprotectin is raised in endogenous posterior uveitis.

Calprotectin, the L1 leucocyte protein, is found in large quantities in the cytosol of granulocytes and monocytes. Plasma calprotectin levels are increased in infections, malignant tumours, vascular insults and various other pathogenic conditions. The authors have investigated plasma calprotectin and ANCA levels in 27 patients with endogenous posterior uveitis (EPU) and six healthy volunteers. Compared to the control values, the mean levels of plasma calprotectin were raised in patients with active uveitis (p<0.005 (ANOVA)). Raised serum ANCA titres, which are also associated with neutrophil activation, were also detected in some patients with EPU but the level of ANCA did not correlate with that of calprotectin. The authors suggest that measurement of plasma calprotectin may be a sensitive indicator of disease activity in patients with endogenous posterior uveitis.

Calprotectin-mediated zinc chelation as a biostatic mechanism in host defence.

The S-100 Ca2+ binding protein, calprotectin, isolated from neutrophil lysates, has been reported to exhibit zinc reversible biostatic activity in vitro. We verified these findings with C. albicans and investigated whether the growth inhibition resulted from zinc deprivation due to chelation by calprotectin. Calprotectin concentrations of 250 micrograms/ml significantly inhibited the growth of C. albicans. This was reversed by supplementing culture medium with 10 microM ZnSO4. Incubation of calprotectin in culture medium for 24 h prior to inoculation significantly reduced the minimum inhibitory concentration. When this latter medium was ultrafiltered to remove the calprotectin and then inoculated with C. albicans, significant growth inhibition was still present: again it was reversed by zinc. These findings implicate zinc chelation as a novel, potentially important host defence function of an abundant neutrophil protein.