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Journal of Immunology Research
Volume 2019, Article ID 4783018, 10 pages
https://doi.org/10.1155/2019/4783018
Research Article

Myeloperoxidase and Eosinophil Peroxidase Inhibit Endotoxin Activity and Increase Mouse Survival in a Lipopolysaccharide Lethal Dose 90% Model

1Department of Pathology, Creighton University School of Medicine, Omaha, NE 68124, USA
2Exoxemis, Inc., Omaha, NE 68110, USA
3Concord Biosciences, LLC, Concord, OH 44077, USA

Correspondence should be addressed to Robert C. Allen; ude.nothgierc@nellatrebor

Received 25 February 2019; Revised 21 July 2019; Accepted 20 August 2019; Published 30 September 2019

Academic Editor: Douglas C. Hooper

Copyright © 2019 Robert C. Allen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Myeloperoxidase (MPO) and eosinophil peroxidase (EPO) are cationic haloperoxidases with potent microbicidal and detoxifying activities. MPO selectively binds to and kills some Gram-positive bacteria (GPB) and all Gram-negative bacteria (GNB) tested. GNB contain endotoxin, i.e., lipopolysaccharide (LPS) comprising a toxic lipid A component. The possibility that MPO and EPO bind and inhibit the endotoxin of GNB was tested by mixing MPO or EPO with LPS or lipid A and measuring for inhibition of endotoxin activity using the chromogenic Limulus amebocyte lysate (LAL) assay. The endotoxin-inhibiting activities of MPO and EPO were also tested in vivo using an LPS 90% lethal dose (LD90) mouse model studied over a five-day period. Mixing MPO or EPO with a fixed quantity of LPS from Escherichia coli O55:B5 or with diphosphoryl lipid A from E. coli F583 inhibited LAL endotoxin activity in proportion to the natural log of the MPO or EPO concentration. MPO and EPO enzymatic activities were not required for inhibition, and MPO haloperoxidase action did not increase endotoxin inhibition. Both MPO and EPO increased mouse survival in the LPS LD90 model. In conclusion, MPO and EPO nonenzymatically inhibited in vitro endotoxin activity using the LAL assay, and MPO and high-dose EPO significantly increased mouse survival in a LPS LD90 model, and such survival was increased in a dose-dependent manner.