J Innate Immun 2010;2:508–521

Specificity in Killing Pathogens Is Mediated by Distinct Repertoires of Human Neutrophil Peptides

Cederlund A.a · Agerberth B.a · Bergman P.b, c
aDepartment of Medical Biochemistry and Biophysics, Karolinska Institutet, bDepartment of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet, Karolinska University Hospital Huddinge and cDepartment of Medicine, Centre for Infectious Medicine (CIM), Karolinska University Hospital, Stockholm, Sweden
email Corresponding Author

 goto top of outline Key Words

  • Neutrophil
  • Polymorphonuclear leukocytes
  • Innate immunity
  • Mucosal immunity
  • Fungal infections
  • Bacterial infections
  • Moraxella catarrhalis
  • Staphylococcus aureus
  • Haemophilus influenzae
  • Candida albicans

 goto top of outline 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.

Copyright © 2010 S. Karger AG, Basel

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 goto top of outline Author Contacts

Dr. Peter Bergman
Department of Laboratory Medicine, Division of Clinical Microbiology F68
Karolinska Institutet and Karolinska University Hospital, Huddinge
SE–14186 Stockholm (Sweden)
Tel. +46 8 5858 0000, Fax +46 8 5858 1305, E-Mail peter.bergman@ki.se

 goto top of outline Article Information

Received: April 20, 2010
Accepted after revision: June 22, 2010
Published online: September 4, 2010
Number of Print Pages : 14
Number of Figures : 6, Number of Tables : 2, Number of References : 44

 goto top of outline Publication Details

Journal of Innate Immunity

Vol. 2, No. 6, Year 2010 (Cover Date: October 2010)

Journal Editor: Herwald H. (Lund), Egesten A. (Lund)
ISSN: 1662-811X (Print), eISSN: 1662-8128 (Online)

For additional information: http://www.karger.com/JIN

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