| LL-37 directs macrophage differentiation toward macrophages with a proinflammatory signature. | |
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MedLine Citation:
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PMID: 20610648 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The human cathelicidin LL-37 has broad-spectrum antimicrobial activity. It also participates at the interface of innate and adaptive immunity by chemoattracting immune effector cells, modulating the production of a variety of inflammatory mediators by different cell types, and regulating the differentiation of monocytes into dendritic cells. In this study, we investigated the effects of LL-37 on the differentiation of human monocytes into anti-inflammatory macrophages (MPhi-2; driven by M-CSF) versus proinflammatory macrophages (MPhi-1; driven by GM-CSF) as well as on fully differentiated MPhi-1 and MPhi-2. Results revealed that monocytes cultured with M-CSF in the presence of LL-37 resulted in macrophages displaying a proinflammatory signature, namely, low expression of CD163 and little IL-10 and profound IL-12p40 production on LPS stimulation. The effects of LL-37 on M-CSF-driven macrophage differentiation were dose- and time-dependent with maximal effects observed at 10 microg/ml when the peptide was present from the start of the cultures. The peptide enhanced the GM-CSF-driven macrophage differentiation. Exposure of fully differentiated MPhi-2 to LL-37 for 6 d resulted in macrophages that produced less IL-10 and more IL-12p40 on LPS stimulation than control MPhi-2. In contrast, LL-37 had no effect on fully differentiated MPhi-1. Peptide mapping using a set of 16 overlapping 22-mer peptides covering the complete LL-37 sequence revealed that the C-terminal portion of LL-37 is responsible for directing macrophage differentiation. Our results furthermore indicate that the effects of LL-37 on macrophage differentiation required internalization of the peptide. Together, we conclude that LL-37 directs macrophage differentiation toward macrophages with a proinflammatory signature. |
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Authors:
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Anne M van der Does; Henry Beekhuizen; Bep Ravensbergen; Tim Vos; Tom H M Ottenhoff; Jaap T van Dissel; Jan W Drijfhout; Pieter S Hiemstra; Peter H Nibbering |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-07-07 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 185 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-27 Completed Date: 2010-09-08 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 1442-9 Citation Subset: AIM; IM |
Affiliation:
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Department of Infectious Diseases, Center for Infectious Diseases, Leiden University Medical Center, C5-P, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Antimicrobial Cationic Peptides / physiology* Bacterial Infections / immunology, pathology, prevention & control Cell Differentiation / immunology* Cells, Cultured Homeostasis / immunology Humans Inflammation / immunology, microbiology, prevention & control Inflammation Mediators / physiology* Interleukin-10 / antagonists & inhibitors, biosynthesis Macrophage Colony-Stimulating Factor / physiology Macrophages / classification, immunology*, pathology* Molecular Sequence Data Monocytes / cytology, immunology Mycobacterium tuberculosis / immunology |
| Chemical | |
Reg. No./Substance:
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0/Antimicrobial Cationic Peptides; 0/Inflammation Mediators; 130068-27-8/Interleukin-10; 143108-26-3/CAP18 lipopolysaccharide-binding protein; 81627-83-0/Macrophage Colony-Stimulating Factor |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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