Antimicrobial Activity of an Abundant Calcium-Binding Protein in the Cytoplasm of Human Neutrophils

Abstract

Studies of experimental infections in animals indicate that phagocytic cells may sometimes control infective foci without actually ingesting or contacting the invading microorganisms. In the present study, an effective inhibitor of Candida albicans growth, previously detected in neutrophils cytoplasm and found to be released only after lysis of the cells, was identified as an abundant calcium-binding protein originally described in neutrophils as the L1 myelomonocytic antigen or the cystic fibrosis antigen. This substance was demonstrated also to have static activity against several other important human pathogens, including Aspergillus fumigatus, Staphylococcus aureus, and Escherichia coli. Growth of the various microorganisms was inhibited to considerably different degrees by the neutrophil protein, with the effects on S. aureus (the least responsive organism) being significantly enhance by addition of calcium to the medium. These findings suggest that after its release by the death of neutrophils at sites of tissue infection, this abundant calcium-binding protein could have a host defense function by controlling the growth of pathogenic microorganisms that escape being killed initially and would otherwise be free to proliferate.

Ubiquicidin, a novel murine microbicidal protein present in the cytosolic fraction of macrophages

“…Currently it is not clear whether macrophages secrete ubiquicidin. The cytosolic fraction of human neutrophils also contains an antimicrobial compound, the calprotectin complex [4,5]. Based on its relative molecular mass and amino-terminal amino acid sequence, it is unlikely that ubiquicidin is the murine equivalent of one of the components of the human calprotectin complex.…”

“…On phagocytosis of microorganisms by neutrophils, these granule-associated polypeptides are transferred to the phagolysosome where they can kill ingested microorganisms. In addition to granule-associated antimicrobial polypeptides, neutrophils also contain a cytosolic antimicrobial protein called calprotectin [4,5].…”

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

“…The antifungal action of this protein complex was described earlier 13,14) : calprotectin suppresses the growth of yeast and fungi. The minimum effective concentration against the growth of Candida albicans is between 10 and 20 mg/ml.…”

“…Therefore, it has been reported that the concentration of calprotectin increases in extracellular fluid in various inflammatory conditions (see below), suggesting that the factor has important functions influencing the inflammatory processes. Evidence that unravels the novel functions of calprotectin is now accumulating: its extracellular functions, including antimicrobial activity, 13,14) and its regulatory activities towards cells which participate in inflammation or immunological reactions, [15][16][17][18][19] were suggested [also see reviews [20][21][22]. The exact physiological role(s) of this protein complex, however, awaits further investigation.…”

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.…”