气候变化领域集成服务门户(CCPortal): Cathelicidin and PMB neutralize endotoxins by multifactorial mechanisms including LPS interaction and targeting of host cell membranes

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DOI	10.1073/pnas.2101721118
	Cathelicidin and PMB neutralize endotoxins by multifactorial mechanisms including LPS interaction and targeting of host cell membranes
	Schromm A.B.; Paulowski L.; Kaconis Y.; Kopp F.; Koistinen M.; Donoghue A.; Keese S.; Nehls C.; Wernecke J.; Garidel P.; Sevcsik E.; Lohner K.; Sanchez-Gomez S.; Martinez-De-Tejada G.; Brandenburg K.; Brameshuber M.; Schütz G.J.; Andrä J.; Gutsmann T.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:27
英文摘要	Antimicrobial peptides (AMPs) contribute to an effective protection against infections. The antibacterial function of AMPs depends on their interactions with microbial membranes and lipids, such as lipopolysaccharide (LPS; endotoxin). Hyperinflammation induced by endotoxin is a key factor in bacterial sepsis and many other human diseases. Here, we provide a comprehensive profile of peptide-mediated LPS neutralization by systematic analysis of the effects of a set of AMPs and the peptide antibiotic polymyxin B (PMB) on the physicochemistry of endotoxin, macrophage activation, and lethality in mice. Mechanistic studies revealed that the host defense peptide LL-32 and PMB each reduce LPS-mediated activation also via a direct interaction of the peptides with the host cell. As a biophysical basis, we demonstrate modifications of the structure of cholesterol-rich membrane domains and the association of glycosylphosphatidylinositol (GPI)-anchored proteins. Our discovery of a host cell-directed mechanism of immune control contributes an important aspect in the development and therapeutic use of AMPs. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Antimicrobial peptides; Endotoxin; Hyperinflammation; Immune regulation; Membrane domains
语种	英语
scopus关键词	cathelicidin; endotoxin; glycosylphosphatidylinositol anchored protein; lipopolysaccharide; polymyxin B; animal experiment; Article; cell membrane; controlled study; drug targeting; female; immunoregulation; lethality; macrophage activation; mouse; nonhuman; physical chemistry; protein domain
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/238876
作者单位	Division of Immunobiophysics, Research Center Borstel, Leibniz Lung Center, Borstel, D-23845, Germany; Division of Biophysics, Research Center Borstel, Leibniz Lung Center, Borstel, D-23845, Germany; Deutsches Elektronen-Synchrotron, Hamburg, D-22607, Germany; Biophysikalische Chemie, Martin-Luther-Universität Halle-Wittenberg, Halle, D-06108, Germany; Institute of Applied Physics, TU Wien, Vienna, 1040, Austria; Institute of Molecular Biosciences, Biophysics Division, University of Graz, Graz, A-8010, Austria; BioTechMed-Graz, Graz, A-8010, Austria; Department of Microbiology and Parasitology, University of Navarra, Pamplona, E-31008, Spain; Navarra Institute for Health Research, Pamplona, E-31008, Spain; Department of Biotechnology, Faculty of Life Sciences, Hamburg University of Applied Sciences, Hamburg, D-21033, Germany
推荐引用方式 GB/T 7714	Schromm A.B.,Paulowski L.,Kaconis Y.,et al. Cathelicidin and PMB neutralize endotoxins by multifactorial mechanisms including LPS interaction and targeting of host cell membranes[J],2021,118(27).
APA	Schromm A.B..,Paulowski L..,Kaconis Y..,Kopp F..,Koistinen M..,...&Gutsmann T..(2021).Cathelicidin and PMB neutralize endotoxins by multifactorial mechanisms including LPS interaction and targeting of host cell membranes.Proceedings of the National Academy of Sciences of the United States of America,118(27).
MLA	Schromm A.B.,et al."Cathelicidin and PMB neutralize endotoxins by multifactorial mechanisms including LPS interaction and targeting of host cell membranes".Proceedings of the National Academy of Sciences of the United States of America 118.27(2021).