title: Specificity in killing pathogens is mediated by distinct repertoires of human neutrophil peptides.
abstract: Neutrophil-derived antimicrobial peptides and proteins (AMPs) play an important role in the defense against microbes. Absence of defense is illustrated by neutropenic patients with frequent bacterial and fungal infections. However, the specificity of the antimicrobial effects has not been adequately described. We set out to determine the specific antimicrobial pattern of polypeptides in neutrophils (polymorphonuclear leukocytes, PMNs) against 4 potential human pathogens: Moraxella catarrhalis, Staphylococcus aureus, Haemophilus influenzae and Candida albicans. Protein extracts of human PMNs were separated using high-performance liquid chromatography and fractions were assayed for antimicrobial activity. Fractions displaying antimicrobial activity were separated on SDS-PAGE and characterized using MALDI-MS. Depletion experiments were utilized to determine the contribution of each AMP to the antimicrobial effect. Among the identified AMPs, α-defensins 1-3, azurocidin, LL-37, lysozyme, calprotectin and lactotransferrin were studied in detail. We found a divergent pattern of killing, that is, certain peptides and proteins exhibited selective activity against specific pathogens, while others displayed a broader antimicrobial activity. α-Defensins, LL-37 and calprotectin were active against all species, while lactotransferrin exclusively inhibited growth of S. aureus. Conversely, azurocidin was active against all species except S. aureus. Our observations may shed light on bacterial resistance to AMPs and on the elimination of specific bacterial communities on mucosal surfaces.
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Andreas
authors.initials: A
authors.lastname: Cederlund
authors.forename: Birgitta
authors.initials: B
authors.lastname: Agerberth
authors.forename: Peter
authors.initials: P
authors.lastname: Bergman
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology*; D001798:Blood Proteins / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects / Q000254:growth & development / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology*; D048708:Cell Growth Processes / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D006193:Haemophilus influenzae / Q000187:drug effects / Q000254:growth & development / Q000276:immunology*; D054884:Host-Pathogen Interactions; D006801:Humans; D018928:Immunity, Mucosal; D007781:Lactoferrin / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D001936:Moraxella catarrhalis / Q000187:drug effects / Q000254:growth & development / Q000276:immunology*; D013045:Species Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development / Q000276:immunology*; D023084:alpha-Defensins / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: C062991:AZU1 protein, human; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D002352:Carrier Proteins; D023084:alpha-Defensins; D007781:Lactoferrin