A 17-kDa Fragment of Lactoferrin Associates With the Termination of Inflammation and Peptides Within Promote Resolution

dc.contributor.authorLutaty, Aviv
dc.contributor.authorSoboh, Soaad
dc.contributor.authorSchif-Zuck, Sagie
dc.contributor.authorZeituni-Timor, Orly
dc.contributor.authorRostoker, Ran
dc.contributor.authorPodolska, Malgorzata J.
dc.contributor.authorSchauer, Christine
dc.contributor.authorHerrmann, Martin
dc.contributor.authorMuñoz, Luis E.
dc.contributor.authorAriel, Amiram
dc.date.accessioned2019-09-03
dc.date.available2023-10-09T15:18:13Z
dc.date.created2018
dc.date.issued2019-09-03
dc.description.abstractDuring the resolution of inflammation, macrophages engulf apoptotic polymorphonuclear cells (PMN) and can accumulate large numbers of their corpses. Here, we report that resolution phase macrophages acquire the neutrophil-derived glycoprotein lactoferrin (Lf) and fragments thereof in vivo and ex vivo. During the onset and resolving phases of inflammation in murine peritonitis and bovine mastitis, Lf fragments of 15 and 17 kDa occurred in various body fluids, and the murine fragmentation, accumulation, and release were mediated initially by neutrophils and later by efferocytic macrophages. The 17-kDa fragment contained two bioactive tripeptides, FKD and FKE that promoted resolution phase macrophage conversion to a pro-resolving phenotype. This resulted in a reduction in peritoneal macrophage numbers and an increase in the CD11blow subset of these cells. Moreover, FKE, but not FKD, peptides enhanced efferocytosis of apoptotic PMN, reduced TNFα and interleukin (IL)-6, and increased IL-10 secretion by lipopolysaccharide-stimulated macrophages ex vivo. In addition, FKE promoted neutrophil-mediated resolution at high concentrations (100 µM) by enhancing the formation of cytokine-scavenging aggregated NETs (tophi) at a low cellular density. Thus, PMN Lf is processed, acquired, and “recycled” by neutrophils and macrophages during inflammation resolution to generate fragments and peptides with paramount pro-resolving activities.en
dc.identifier.citationFrontiers in Immunology 9 (2018). <https://www.frontiersin.org/articles/10.3389/fimmu.2018.00644/full>
dc.identifier.doihttps://doi.org/10.3389/fimmu.2018.00644
dc.identifier.issn1664-3224
dc.identifier.opus-id11907
dc.identifier.urihttps://open.fau.de/handle/openfau/11907
dc.identifier.urnurn:nbn:de:bvb:29-opus4-119073
dc.language.isoen
dc.publisherFrontiers Media S.A.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/deed.de
dc.subjectresolution of inflammation
dc.subjectlactoferrin
dc.subjectmacrophages
dc.subjectefferocytosis
dc.subjectNETosis
dc.subject.ddcDDC Classification::6 Technik, Medizin, angewandte Wissenschaften :: 61 Medizin und Gesundheit :: 610 Medizin und Gesundheit
dc.titleA 17-kDa Fragment of Lactoferrin Associates With the Termination of Inflammation and Peptides Within Promote Resolutionen
dc.typearticle
dcterms.publisherFriedrich-Alexander-Universität Erlangen-Nürnberg (FAU)
local.date.prevpublished2018-03-28
local.journal.titleFrontiers in Immunology
local.journal.volume9
local.sendToDnbfree*
local.subject.fakultaetMedizinische Fakultät
local.subject.importimport
local.subject.sammlungUniversität Erlangen-Nürnberg / Eingespielte Open Access Artikel / Eingespielte Open Access Artikel 2019
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