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Published on: January 7, 2019
Cooperative Function of LL-37 and HNP1 Protects Mammalian Cell Membranes from Lysis
1Department of Physical Chemistry, University of Geneva, Geneva, Switzerland.
Abstract:
LL-37, cleaved from human cathelicidin, and human neutrophil peptide-1 (HNP1) from the defensin family are antimicrobial peptides that are occasionally co-released from neutrophils, which synergistically kill bacteria. We report that this couple presents another type of cooperativity against host eukaryotic cells, in which they antagonistically minimize cytotoxicity by protecting membranes from lysis. Our results describe the potential of the LL-37/HNP1 cooperativity that switches from membrane-destructive to membrane-protective functions, depending on whether the target is an enemy or a host.
Insights
Antimicrobial peptides LL-37 and HNP1 exhibit dual cooperativity. They synergistically kill bacteria but protect host cells by preventing membrane lysis, demonstrating context-dependent functions.
Area of Science:
- Immunology
- Biochemistry
- Cell Biology
Background:
- LL-37 (human cathelicidin) and human neutrophil peptide-1 (HNP1) are antimicrobial peptides.
- These peptides are co-released by neutrophils and exhibit synergistic antibacterial activity.
- Neutrophils play a crucial role in innate immunity against microbial infections.
Purpose of the Study:
- To investigate the cooperative functions of LL-37 and HNP1 beyond bacterial killing.
- To explore the impact of LL-37/HNP1 interaction on host eukaryotic cells.
- To understand the switch in function from membrane-destructive to membrane-protective.
Main Methods:
- Investigated the effects of co-applied LL-37 and HNP1 on bacterial and eukaryotic cell membranes.
- Utilized biophysical techniques to assess membrane integrity and lysis.
- Analyzed the functional outcomes of peptide interactions in different cellular contexts.
Main Results:
- LL-37 and HNP1 demonstrate cooperative membrane protection against lysis in host eukaryotic cells.
- This protective effect antagonizes their membrane-disruptive action seen against bacteria.
- The dual cooperativity is dependent on the target cell type (bacterial vs. host).
Conclusions:
- The LL-37/HNP1 cooperative interaction exhibits context-dependent functionality.
- This peptide pair can switch from being bactericidal to cytoprotective.
- Findings reveal a novel mechanism for host cell defense mediated by antimicrobial peptides.
