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 in vitro, ex vivo, and in vivo. In this study, the...

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Main Authors: Hansen, Finja C., Strömdahl, Ann-Charlotte, Mörgelin, Matthias, Schmidtchen, Artur, van der Plas, Mariena J. A.
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Article
Language:English
Published: 2017
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Online Access:https://hdl.handle.net/10356/80519
http://hdl.handle.net/10220/43423
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-805192020-11-01T05:17:09Z Thrombin-Derived Host-Defense Peptides Modulate Monocyte/Macrophage Inflammatory Responses to Gram-Negative Bacteria Hansen, Finja C. Strömdahl, Ann-Charlotte Mörgelin, Matthias Schmidtchen, Artur van der Plas, Mariena J. A. Lee Kong Chian School of Medicine (LKCMedicine) Host-defense peptides 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 in vitro, ex vivo, and in vivo. 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 Staphylococcus aureus and Pseudomonas aeruginosa, 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 Escherichia coli 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. Published version 2017-07-24T03:04:52Z 2019-12-06T13:51:19Z 2017-07-24T03:04:52Z 2019-12-06T13:51:19Z 2017 Journal Article Hansen, F. C., Strömdahl, A.-C., Mörgelin, M., Schmidtchen, A., & van der Plas, M. J. A. (2017). Thrombin-Derived Host-Defense Peptides Modulate Monocyte/Macrophage Inflammatory Responses to Gram-Negative Bacteria. Frontiers in Immunology, 8, 843-. https://hdl.handle.net/10356/80519 http://hdl.handle.net/10220/43423 10.3389/fimmu.2017.00843 en Frontiers in Immunology © 2017 Hansen, Strömdahl, Mörgelin, Schmidtchen and van der Plas. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. 11 p. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Host-defense peptides
Gram-negative bacteria
spellingShingle Host-defense peptides
Gram-negative bacteria
Hansen, Finja C.
Strömdahl, Ann-Charlotte
Mörgelin, Matthias
Schmidtchen, Artur
van der Plas, Mariena J. A.
Thrombin-Derived Host-Defense Peptides Modulate Monocyte/Macrophage Inflammatory Responses to Gram-Negative Bacteria
description 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 in vitro, ex vivo, and in vivo. 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 Staphylococcus aureus and Pseudomonas aeruginosa, 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 Escherichia coli 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.
author2 Lee Kong Chian School of Medicine (LKCMedicine)
author_facet Lee Kong Chian School of Medicine (LKCMedicine)
Hansen, Finja C.
Strömdahl, Ann-Charlotte
Mörgelin, Matthias
Schmidtchen, Artur
van der Plas, Mariena J. A.
format Article
author Hansen, Finja C.
Strömdahl, Ann-Charlotte
Mörgelin, Matthias
Schmidtchen, Artur
van der Plas, Mariena J. A.
author_sort Hansen, Finja C.
title Thrombin-Derived Host-Defense Peptides Modulate Monocyte/Macrophage Inflammatory Responses to Gram-Negative Bacteria
title_short Thrombin-Derived Host-Defense Peptides Modulate Monocyte/Macrophage Inflammatory Responses to Gram-Negative Bacteria
title_full Thrombin-Derived Host-Defense Peptides Modulate Monocyte/Macrophage Inflammatory Responses to Gram-Negative Bacteria
title_fullStr Thrombin-Derived Host-Defense Peptides Modulate Monocyte/Macrophage Inflammatory Responses to Gram-Negative Bacteria
title_full_unstemmed Thrombin-Derived Host-Defense Peptides Modulate Monocyte/Macrophage Inflammatory Responses to Gram-Negative Bacteria
title_sort thrombin-derived host-defense peptides modulate monocyte/macrophage inflammatory responses to gram-negative bacteria
publishDate 2017
url https://hdl.handle.net/10356/80519
http://hdl.handle.net/10220/43423
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