The Zinc-Reversible Antimicrobial Activity of Neutrophil Lysates and Abscess Fluid Supernatants

Abstract

There is some evidence to suggest that microbial growth inhibition may occur in chronic abscesses. A substance perhaps responsible for this phenomenon is calprotectin, a neutrophil cytoplasmic protein that inhibits microbial growth and that belongs to a class of proteins often having specific binding sites for zinc. In the present study, the suppressive effects of either human or mouse neutrophil lysates on Candida albicans growth were found to be completely reversed by micromolar quantities of zinc but not by iron or other trace elements. Similarly, supernatants of exudates from experimental abscesses in mice or from clinical specimens of abscesses in humans markedly inhibited the proliferation of C. albicans, and this effect was also completely reversed by zinc. A protein complex characteristic of calprotectin was identified in the abscess fluids. Preparations of the neutrophil growth-inhibiting protein, containing predominantly calprotectin, were shown to have zinc-binding activity by a dialysis technique. These findings suggest that the major mechanism of C. albicans growth inhibition by abscess fluids is through competition for zinc by a cytoplasmic protein apparently released from dying neutrophils.

Inhibitory Role of Neutrophils on Influenza Virus Multiplication in the Lungs of Mice

“…However, the antiviral mechanism of neutrophils in host defense has not been investigated in detail. Recent studies indicated that neutrophils produced calprotectin as an antibacterial and antitumor protein (5,24,32,42), and that the antibacterial and antitumor activities of calprotectin were reversibly reduced by ZnS0 4 (5, 32). To assess the involvement of calprotectin in the inhibitory effect of neutrophils on influenza virus propagation, neutrophils and ZnS04 were added to MOCK cell cultures infected with influenza virus.…”

“…This study was performed by applying neutrophilic leukocytosis in tumor-bearing mice and neutrophil activation by tMLP in vivo to elucidate the roles of neutrophils as an effector cell population in the host defense against influenza virus infection. Furthermore, recent studies have indicated that neutrophils produce cal protectin as an antibacterial, antifungal, and antitumor protein (10,24,32,42), suggesting that calprotectin has a new mechanism of action based on a depletion of Zn ++• In this study, the contribution of calprotectin to the inhibitory effect of neutrophils on influenza virus propagation was also investigated.…”

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

“…The antifungal activity of calprotectin is inhibited by the presence of zinc ion and the factor has a zinc-binding property 50,51) ; in fact, there are zinc-binding motifs in the subunit peptides. 52) This suggests that the factor withholds zinc from the growth media of fungi, because fungi strongly require zinc for their growth.…”

Blockade of S100A8 and S100A9 Suppresses Neutrophil Migration in Response to Lipopolysaccharide

“…Together, these activities indicate a putative role in regulating leukocyte migration to inflammatory sites. S100A8/A9 is also known to inhibit microbial growth, presumably by chelating zinc (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33) and to inhibit bacterial adhesion to mucosal epithelial cells (34). Thus, it is reasonable to propose a role in innate immune responses to bacterial infections for these molecules.…”