Dataset Information

A 17 kDa fragment of lactoferrin associates with the termination of inflammation and peptides within promote resolution

ABSTRACT: During 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) in vivo and ex vivo and process it to short fragments. 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 and release were mediated by macrophages. The 17 kDa fragment contained two bioactive tripeptides, FKD and FKE that promoted human macrophage reprogramming to a pro-resolving phenotype. At low concentrations (1-10 M) this was reflected by inhibition of LPS-induced TNFand IL-6 secretion and increased IL-10 levels. Both peptides inhibited ERK and cJun activation following macrophage exposure to LPS. In addition, FKD, and to a lesser extent FKE, promoted neutrophil-mediated resolution at high concentrations (30-100 M) by enhancing the formation of cytokine-scavenging aggregated NETs at low cellular density. Thus, PMN lactoferrin is acquired, processed and

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Bos Taurus (bovine)

TISSUE(S): Milk

SUBMITTER: Sagie Schif

LAB HEAD: Amiram Ariel

PROVIDER: PXD009190 | Pride | 2018-03-20

REPOSITORIES: Pride

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

Lutaty Aviv A Soboh Soaad S Schif-Zuck Sagie S Zeituni-Timor Orly O Rostoker Ran R Podolska Malgorzata J MJ Schauer Christine C Herrmann Martin M Muñoz Luis E LE Ariel Amiram A

Frontiers in immunology 20180328

During 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 <i>in vivo</i> and <i>ex vivo</i>. 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 fragment ...[more]

PMID: 29643857

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Project description:Dunster2014 - WBC Interactions (Model1) This is a sub-model of a three-step inflammatory response modelling study. The model includes distinct populations of white blood cells namely, macrophages and active and apoptotic neutrophil populations. Neutrophil apoptosis rate is predicted to be crucial for the qualitative nature of the system. This model is described in the article: The resolution of inflammation: a mathematical model of neutrophil and macrophage interactions. Dunster JL, Byrne HM, King JR. Bull. Math. Biol. 2014 Aug; 76(8): 1953-1980 Abstract: There is growing interest in inflammation due to its involvement in many diverse medical conditions, including Alzheimer's disease, cancer, arthritis and asthma. The traditional view that resolution of inflammation is a passive process is now being superceded by an alternative hypothesis whereby its resolution is an active, anti-inflammatory process that can be manipulated therapeutically. This shift in mindset has stimulated a resurgence of interest in the biological mechanisms by which inflammation resolves. The anti-inflammatory processes central to the resolution of inflammation revolve around macrophages and are closely related to pro-inflammatory processes mediated by neutrophils and their ability to damage healthy tissue. We develop a spatially averaged model of inflammation centring on its resolution, accounting for populations of neutrophils and macrophages and incorporating both pro- and anti-inflammatory processes. Our ordinary differential equation model exhibits two outcomes that we relate to healthy and unhealthy states. We use bifurcation analysis to investigate how variation in the system parameters affects its outcome. We find that therapeutic manipulation of the rate of macrophage phagocytosis can aid in resolving inflammation but success is critically dependent on the rate of neutrophil apoptosis. Indeed our model predicts that an effective treatment protocol would take a dual approach, targeting macrophage phagocytosis alongside neutrophil apoptosis. This model is hosted on BioModels Database and identified by: BIOMD0000000616. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

			Action	DRS
	Seq31295_E2O2-01.msf	Msf
	Seq31295_E2O2.raw	Raw
	Seq31296_E2O2-01.msf	Msf
	Seq31296_E2O2.raw	Raw