Calprotectin‐Mediated Zinc Chelation as a Biostatic Mechanism in Host Defence

Abstract

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.

Calprotectin (S100A8/S100A9), an Inflammatory Protein Complex from Neutrophils with a Broad Apoptosis-Inducing Activity

“…However, it is easy to imagine that there may be a higher concentration of calprotectin in the interstitial fluid of a limited inflammatory area in which neutrophils have extensively accumulated. This might be supported by the findings that Ͼ1 mg/ml of calprotectin is present in the abscess fluids of patients, 41) and which are possibly composed of very high amounts of fresh or effete neutrophils. In any event, calprotectin has been viewed as a good clinical marker for diagnosis, since there is a tendency for an increase in extracellular calprotectin correlate with the inflammatory state of a disease.…”

“…However, it is probable that in a local inflammatory site where a great number of neutrophils have accumulated, the calprotectin concentration is high enough to exert these effects. In this respect, it is to be noted that abscess sites of contain 1-20 mg/ml of calprotectin, 41) which may inhibit growth and induce the apoptosis of fibroblasts or other cells surrounding the abscess in vivo.…”

“…52) This suggests that the factor withholds zinc from the growth media of fungi, because fungi strongly require zinc for their growth. 41) Several pieces of evidence now point to the deprivation of nutrient zinc as the mechanism of the antifungal action, and it seems that the direct contact of calprotectin with fungal cells is not required for the inhibition of growth. abscess in vivo, because the supernatant of the abscess fluid showed the antifungal activity and was also inhibited by the addition of zinc.…”

“…11,[29][30][31][32][33][34][35][36][37][38][39][40][41] Examples of the inflammatory states in which extracellular calprotectin reportedly increases are depicted in Table 1. The calprotectin-upregulated pathological states were also listed in more detail in a review by Johne et al 21) Berntzen et al reported that in healthy human serum/ plasma, the concentration of calprotectin was less than 1 mg/ml, while the plasma concentration of patients with rheumatoid arthritis (RA) was reportedly increased to approximately 10-fold higher concentrations as mean values.…”

Immunomodulatory Trace Element (Zinc) In HIV Sero Positive Individuals

“…Zinc is required by human beings and pathogens for proliferation. Thus a decreasing plasma zinc levels during acute phase infection is a defense mechanism of human organisms (Clohessy et al, 1995). Beta cell which represents main cells of humoral Immunity and T-cells are reduced during zinc deficiency (Moulder, 1989).…”