HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Bucki, R. Articles by Janmey, P. A. Search for Related Content PubMed PubMed Citation Articles by Bucki, R. Articles by Janmey, P. A.

Release of the antimicrobial peptide LL-37 from DNA/F-actin bundles in cystic fibrosis sputum

Dept of Physiology and the Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA, USA.

CORRESPONDENCE: R. Bucki, Dept of Physiology and the Institute for Medicine and Engineering, University of Pennsylvania, 1010 Vagelos Research Laboratories, 3340 Smith Walk, Philadelphia, PA, 19104 USA. Fax: 1 2155737227. E-mail: buckirob{at}mail.med.upenn.edu

Keywords: Cystic fibrosis, gelsolin, lipopolysaccharide, LL-37 peptide, polyaspartate, recombinant human DNase I

Received: June 20, 2006
Accepted December 16, 2006

Cationic antibacterial peptides (ABPs) are secreted in the airways and function in the first line of defence against infectious agents. They attack multiple molecular targets to cooperatively penetrate and disrupt microbial surfaces and membrane barriers. Antibacterial properties of ABPs, including cathelicidin LL-37, are reduced in cystic fibrosis (CF) airways as a result of direct interaction with DNA and filamentous (F)-actin.

Microscopic evaluation of a mixed solution of DNA and F-actin, after the addition of rhodamine-B-labelled LL-37 peptide, revealed the presence of a bundle structure similar to that present in CF sputum. Analysis of CF sputum after centrifugation showed that LL-37 was mostly bound to components of the pellet fraction containing DNA, F-actin and cell remnants. Factors that dissolve DNA/actin bundles and fluidise CF sputum, such as Dornase alfa (recombinant human DNase I), gelsolin, polyaspartate or their combinations, increased the amount of LL-37 peptide detected in the supernatant of CF sputum.

The presence of the bacterial endotoxin lipopolysaccharide (LPS) in CF sputum and the ability of LPS to inhibit the antibacterial activity of LL-37 suggests that inactivation of LL-37 function in CF sputum partially results from its interaction with LPS. LL-37–LPS interaction was prevented by an LPS-binding protein (LBP)-derived peptide known for its ability to neutralise LPS, whereas LBPW91A, a mutant peptide that lacks ability to bind LPS, had no effect.

A combination of factors that dissolve DNA/filamentous-actin aggregates together with lipopolysaccharide-binding agents may represent a potential treatment for the chronic infections that occur in cystic fibrosis airways.

This article has been cited by other articles:

				L. K. Sanders, W. Xian, C. Guaqueta, M. J. Strohman, C. R. Vrasich, E. Luijten, and G. C. L. Wong Control of electrostatic interactions between F-actin and genetically modified lysozyme in aqueous media PNAS, October 9, 2007; 104(41): 15994 - 15999. [Abstract] [Full Text] [PDF]