The antimicrobial peptide cathelicidin interacts with airway mucus.
Felgentreff. Kerstin K; Beisswenger. Christoph C; Griese. Matthias M; Gulder. Tanja T; Bringmann. Gerhard G; Bals. Robert R
Key Findings
- LL‑37 binds electrostatically to negatively charged mucins
- Mucins cause LL‑37 to adopt an alpha‑helical shape
- Binding to mucins significantly lowers LL‑37’s antibacterial activity against Pseudomonas aeruginosa and Streptococcus pneumoniae
- A substantial portion of LL‑37 in human airway secretions is already bound to high‑molecular‑weight mucus components
Practical Outcomes
- If you’re considering LL‑37 for lung health or as an inhaled antimicrobial, mucus can reduce its effectiveness. Strategies that reduce mucus binding—like using mucolytic agents or delivery systems that bypass mucus—might improve outcomes. This insight helps refine dosing or formulation choices, but the study doesn’t provide a ready‑to‑use protocol.
Summary
The study shows that the natural antimicrobial peptide LL‑37 sticks to the sticky proteins (mucins) in airway mucus because they have opposite charges. This binding changes the shape of LL‑37 and makes it less able to kill common lung bacteria. In real human airway samples, a good chunk of LL‑37 is already stuck to these big mucus molecules, meaning its activity can be dampened by the mucus itself.
Abstract
Antimicrobial peptides (AMPs) and mucins are components of airway secretions and both contribute to the innate host defense system. At neutral pH, AMPs are positively charged, mucins negatively. It was the aim of the study to test whether these opposite charges result in interactions between AMPs and mucins. We measured binding of mucins isolated from porcine gastric mucosa to the cathelicidin LL-37 coated to multiwell plates and found that LL-37 electrostatically interacts with mucins. Circular dichroism spectra of the peptide revealed the induction of alpha-helical conformation by mucins. Addition of mucins to solutions of LL-37 significantly decreased the antimicrobial activity of the peptide against Pseudomonas aeruginosa and Streptococcus pneumoniae. We then tested whether LL-37 is bound to mucins in airway secretions from human subjects and found that a significant proportion of the peptide and its propeptide are bound to high molecular weight components. Together these data show that cationic AMPs interact with anionic mucins in airway secretions. Functions of AMPs are modulated by this interaction.
Study Information
pubmed
2006
2006-09-11T00:00:00.000Z
10.1016/j.peptides.2006.07.018
88
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