Loading…

Thrombin-Derived Host-Defense Peptides Modulate Monocyte/Macrophage Inflammatory Responses to Gram-Negative Bacteria

Host-defense peptides play a fundamental role in the innate immune system by modulating inflammatory responses. Previously, it was shown that the thrombin derived host-defense peptide GKY25 inhibits LPS-induced responses of monocytes and macrophages , and . In this study, the effect of GKY25 on the...

Full description

Saved in:
Bibliographic Details
Published in:Frontiers in immunology 2017-07, Vol.8 (JUL), p.843-843
Main Authors: Hansen, Finja C, Strömdahl, Ann-Charlotte, Mörgelin, Matthias, Schmidtchen, Artur, van der Plas, Mariena J A
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Host-defense peptides play a fundamental role in the innate immune system by modulating inflammatory responses. Previously, it was shown that the thrombin derived host-defense peptide GKY25 inhibits LPS-induced responses of monocytes and macrophages , and . In this study, the effect of GKY25 on the interaction of monocytes/macrophages with Gram-negative bacteria was explored. Electron microscopy analysis showed that fibrin slough from non-healing wounds, colonized with and , contains C-terminal thrombin epitopes associated with these bacteria extracellularly and in phagosomes of leukocytes. Live imaging of RAW 264.7 cell cultures showed binding of GKY25 to BioParticles extracellularly, and colocalization intracellularly. Although peptide binding did not alter the rate of phagocytosis, GKY25 reduced NF-κB/AP-1 activation and subsequent cytokine release in response to both heat-killed and live bacteria. Notably, preincubation of RAW 264.7 cells with peptide did increase BioParticle uptake in a dose-dependent manner. Taken together, the thrombin-derived host-defense peptide GKY25 binds to bacteria extracellularly and colocalizes with bacteria intracellularly, thereby reducing pro-inflammatory responses.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2017.00843