Differential Internalization of Thrombin-Derived Host Defense Peptides into Monocytes and Macrophages.

Autor: Hansen FC; Division of Dermatology and Venereology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden., Nadeem A; Department of Microbiology, Immunology and Glycobiology (MIG), Institute of Laboratory Medicine, Lund University, Lund, Sweden.; Department of Molecular Biology, Umeå University, Umeå, Sweden., Browning KL; LEO Foundation Center for Cutaneous Drug Delivery, Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark., Campana M; ISIS Neutron and Muon Source, Rutherford Appleton Laboratory, Harwell, United Kingdom., Schmidtchen A; Division of Dermatology and Venereology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.; Dermatology, Skåne University Hospital, Lund, Sweden.; Copenhagen Wound Healing Center, Bispebjerg Hospital, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark., van der Plas MJA; Division of Dermatology and Venereology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.; LEO Foundation Center for Cutaneous Drug Delivery, Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark.
Jazyk: angličtina
Zdroj: Journal of innate immunity [J Innate Immun] 2022; Vol. 14 (5), pp. 418-432. Date of Electronic Publication: 2021 Dec 22.
DOI: 10.1159/000520831
Abstrakt: Proteolytic cleavage of thrombin generates C-terminal host defense peptides exerting multiple immunomodulatory effects in response to bacterial stimuli. Previously, we reported that thrombin-derived C-terminal peptides (TCPs) are internalized in monocytes and macrophages in a time- and temperature-dependent manner. In this study, we investigated which endocytosis pathways are responsible for the internalization of TCPs. Using confocal microscopy and flow cytometry, we show that both clathrin-dependent and clathrin-independent pathways are involved in the internalization of the prototypic TCP GKY25 in RAW264.7 and human monocyte-derived M1 macrophages, whereas the uptake of GKY25 in monocytic THP-1 cells is mainly dynamin-dependent. Internalized GKY25 was transported to endosomes and finally lysosomes, where it remained detectable for up to 10 h. Comparison of GKY25 uptake with that of the natural occurring TCPs HVF18 and FYT21 indicates that the pathway of TCP endocytosis is not only cell type-dependent but also depends on the length and composition of the peptide as well as the presence of LPS and bacteria. Finally, using neutron reflectometry, we show that the observed differences between HVF18 and the other 2 TCPs may be explained partially by differences in membrane insertion. Taken together, we show that TCPs are differentially internalized into monocytes and macrophages.
(© 2021 The Author(s). Published by S. Karger AG, Basel.)
Databáze: MEDLINE
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