Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Myeloperoxidase

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (15 December 2022) | Viewed by 18017

Share This Special Issue

Special Issue Editor

Dr. John W. Chen

E-Mail Website
Guest Editor

Institute for Innovation in Imaging and Center for Systems Biology, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
Interests: microglia, macrophages; immune response; inflammation; neuroinflammation; oxidative stress; molecular imaging; neurological diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Myeloperoxidase (MPO) is a highly oxidative enzyme found in many pro-inflammatory myeloid cells. MPO plays important roles in host defense and innate immune response through its catalytic activity and generation of highly reactive species. In addition, MPO also has regulatory roles in modulating the immune response. However, aberrant expression and activation of MPO have been reported in many diseases, including rheumatological, neurological, respiratory, cardiovascular, and oncological diseases. Strategies and drugs have been developed to potentially combat the deleterious effects when MPO is inappropriately present.

This Special Issue, “Myeloperoxidase”, will provide a collection of articles and reviews to summarize the field and explore recent advances in MPO’s biochemistry, molecular and cellular interactions, involvement in the immune response and diseases, and potential impact as a therapeutic target. We warmly welcome contributions related to any of these aspects.

Dr. John W. Chen
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

myeloperoxidase
inflammation
immune response
oxidative stress
innate immunity
pro-inflammatory
neutrophils
macrophages
host defense

Published Papers (7 papers)

Download All Papers

Research

Jump to: Review

13 pages, 1971 KiB

Open AccessArticle

Detrimental Actions of Chlorinated Nucleosides on the Function and Viability of Insulin-Producing Cells

by Inga Sileikaite-Morvaközi, William H. Hansen, Michael J. Davies, Thomas Mandrup-Poulsen and Clare L. Hawkins

Int. J. Mol. Sci. 2023, 24(19), 14585; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241914585 - 26 Sep 2023

Cited by 1 | Viewed by 794

Abstract

Neutrophils are innate immune cells that play a key role in pathogen clearance. They contribute to inflammatory diseases, including diabetes, by releasing pro-inflammatory cytokines, reactive oxygen species, and extracellular traps (NETs). NETs contain a DNA backbone and catalytically active myeloperoxidase (MPO), which produces hypochlorous acid (HOCl). Chlorination of the DNA nucleoside 8-chloro-deoxyguanosine has been reported as an early marker of inflammation in diabetes. In this study, we examined the reactivity of different chlorinated nucleosides, including 5-chloro-(deoxy)cytidine (5ClC, 5CldC), 8-chloro-(deoxy)adenosine (8ClA, 8CldA) and 8-chloro-(deoxy)guanosine (8ClG, 8CldG), with the INS-1E β-cell line. Exposure of INS-1E cells to 5CldC, 8CldA, 8ClA, and 8CldG decreased metabolic activity and intracellular ATP, and, together with 8ClG, induced apoptotic cell death. Exposure to 8ClA, but not the other nucleosides, resulted in sustained endoplasmic reticulum stress, activation of the unfolded protein response, and increased expression of thioredoxin-interacting protein (TXNIP) and heme oxygenase 1 (HO-1). Exposure of INS-1E cells to 5CldC also increased TXNIP and NAD(P)H dehydrogenase quinone 1 (NQO1) expression. In addition, a significant increase in the mRNA expression of NQO1 and GPx4 was seen in INS-1E cells exposed to 8ClG and 8CldA, respectively. However, a significant decrease in intracellular thiols was only observed in INS-1E cells exposed to 8ClG and 8CldG. Finally, a significant decrease in the insulin stimulation index was observed in experiments with all the chlorinated nucleosides, except for 8ClA and 8ClG. Together, these results suggest that increased formation of chlorinated nucleosides during inflammation in diabetes could influence β-cell function and may contribute to disease progression. Full article

(This article belongs to the Special Issue Myeloperoxidase)

► Show Figures

Figure 1

11 pages, 1546 KiB

Open AccessArticle

Myeloperoxidase PET Imaging Tracks Intracellular and Extracellular Treatment Changes in Experimental Myocardial Infarction

by Matthias W. G. Zeller, Cuihua Wang, Edmund J. Keliher, Gregory R. Wojtkiewicz, Aaron Aguirre, Kevin Maresca, Chunyan Su, Leonard Buckbinder, Jing Wang, Matthias Nahrendorf and John W. Chen

Int. J. Mol. Sci. 2023, 24(6), 5704; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24065704 - 16 Mar 2023

Cited by 1 | Viewed by 1402

Abstract

Myeloperoxidase (MPO) is a highly oxidative, pro-inflammatory enzyme involved in post-myocardial infarction (MI) injury and is a potential therapeutic target. While multiple MPO inhibitors have been developed, the lack of an imaging reporter to select appropriate patients and assess therapeutic efficacy has hampered clinical development. Thus, a translational imaging method to detect MPO activity non-invasively would help to better understand the role MPO plays in MI and facilitate novel therapy development and clinical validation. Interestingly, many MPO inhibitors affect both intracellular and extracellular MPO, but previous MPO imaging methods can only report extracellular MPO activity. In this study, we found that an MPO-specific PET imaging agent (¹⁸F-MAPP) can cross cell membranes to report intracellular MPO activity. We showed that ¹⁸F-MAPP can track the treatment effect of an MPO inhibitor (PF-2999) at different doses in experimental MI. The imaging results were corroborated by ex vivo autoradiography and gamma counting data. Furthermore, extracellular and intracellular MPO activity assays revealed that ¹⁸F-MAPP imaging can report the changes induced by PF-2999 on both intracellular and extracellular MPO activities. These findings support ¹⁸F-MAPP as a translational candidate to noninvasively report MPO activity and accelerate drug development against MPO and other related inflammatory targets. Full article

(This article belongs to the Special Issue Myeloperoxidase)

► Show Figures

Figure 1

15 pages, 2045 KiB

Open AccessArticle

Inhibition of Myeloperoxidase Pro-Fibrotic Effect by Noscapine in Equine Endometrium

by Ana Amaral, Nélio Cebola, Anna Szóstek-Mioduchowska, Maria Rosa Rebordão, Paweł Kordowitzki, Dariusz Skarzynski and Graça Ferreira-Dias

Int. J. Mol. Sci. 2023, 24(4), 3593; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24043593 - 10 Feb 2023

Viewed by 1732

Abstract

Myeloperoxidase is an enzyme released by neutrophils when neutrophil extracellular traps (NETs) are formed. Besides myeloperoxidase activity against pathogens, it was also linked to many diseases, including inflammatory and fibrotic ones. Endometrosis is a fibrotic disease of the mare endometrium, with a large impact on their fertility, where myeloperoxidase was shown to induce fibrosis. Noscapine is an alkaloid with a low toxicity, that has been studied as an anti-cancer drug, and more recently as an anti-fibrotic molecule. This work aims to evaluate noscapine inhibition of collagen type 1 (COL1) induced by myeloperoxidase in equine endometrial explants from follicular and mid-luteal phases, at 24 and 48 h of treatment. The transcription of collagen type 1 alpha 2 chain (COL1A2), and COL1 protein relative abundance were evaluated by qPCR and Western blot, respectively. The treatment with myeloperoxidase increased COL1A2 mRNA transcription and COL1 protein, whereas noscapine was able to reduce this effect with respect to COL1A2 mRNA transcription, in a time/estrous cycle phase-dependent manner (in explants from the follicular phase, at 24 h of treatment). Our study indicates that noscapine is a promising drug to be considered as an anti-fibrotic molecule to prevent endometrosis development, making noscapine a strong candidate to be applied in future endometrosis therapies. Full article

(This article belongs to the Special Issue Myeloperoxidase)

► Show Figures

Figure 1

23 pages, 10653 KiB

Open AccessArticle

The Role of Myeloperoxidase in Clozapine-Induced Inflammation: A Mechanistic Update for Idiosyncratic Drug-Induced Agranulocytosis

by Samantha Christine Sernoskie, Alison Jee and Jack Uetrecht

Int. J. Mol. Sci. 2023, 24(2), 1243; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24021243 - 08 Jan 2023

Cited by 3 | Viewed by 3444

Abstract

The risk of idiosyncratic drug-induced agranulocytosis (IDIAG) markedly constrains the use of clozapine, a neuroleptic with unparalleled efficacy. Most clozapine patients experience an early inflammatory response, likely a necessary step in IDIAG onset. However, most patients do not progress to IDIAG, presumably because of the requirement of specific human leukocyte antigen (HLA) haplotypes, T cell receptors, and other unknown factors. We established that clozapine activates inflammasomes and that myeloperoxidase bioactivation of clozapine generates neoantigens, but the connection between these early mechanistic events remained unknown and, thus, was the aim of this work. We found that the myeloperoxidase inhibitor PF-1355 attenuated myeloperoxidase activity in phorbol myristate acetate (PMA)-differentiated THP-1 macrophages, and it also attenuated clozapine-induced release of inflammatory mediators (e.g., IL-1β, CXCL1, and C-reactive protein). In vivo, pretreatment of Sprague Dawley rats with PF-1355 significantly attenuated clozapine-induced increases in neutrophil mobilization from the bone marrow to the blood and spleen, as determined using differential blood counts and flow cytometry. Moreover, the clozapine-triggered release of inflammatory mediators (e.g., IL-1β, calprotectin, CXCL1, and α-1-acid glycoprotein) from the liver, spleen, and bone marrow was dampened by myeloperoxidase inhibition. These data support the working hypothesis that oxidation of clozapine to a reactive metabolite by myeloperoxidase is critical for induction of the inflammatory response to clozapine. Ultimately, a better mechanistic understanding of the early events involved in the immune response to clozapine may elucidate ways to prevent IDIAG, enabling safer, more frequent therapeutic use of this and potentially other highly efficacious drugs. Full article

(This article belongs to the Special Issue Myeloperoxidase)

► Show Figures

Figure 1

12 pages, 1497 KiB

Open AccessArticle

Welding Fume Instillation in Isolated Perfused Mouse Lungs—Effects of Zinc- and Copper-Containing Welding Fumes

by Julia Krabbe, Thomas Kraus, Hanif Krabbe, Christian Martin and Patrick Ziegler

Int. J. Mol. Sci. 2022, 23(16), 9052; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23169052 - 12 Aug 2022

Cited by 3 | Viewed by 1370

Abstract

Zinc- and copper-containing welding fumes can cause systemic inflammation after exposure in humans. Recent ex vivo studies have shown that the observed inflammation originates from exposed immune cells. In vitro studies identified the soluble fraction of metal particles as the main effectors. Isolated perfused mouse lungs (IPLs) were perfused and ventilated for 270 min. Lungs were instilled with saline solution (control), welding fume particle suspension (WFs) or the soluble fraction of the welding fumes (SF-WFs). Bronchoalveolar lavage fluid (BALF) and perfusate samples were analyzed for cytokine levels and lung tissue mRNA expression levels were analyzed via RT-PCR. All lungs instilled with WFs did not complete the experiments due to a fatal reduction in tidal volume. Accordingly, IL-6 and MPO levels were significantly higher in BALF of WF lungs compared to the control. IL-6 and MPO mRNA expression levels were also increased for WFs. Lungs instilled with SF-WFs only showed mild reactions in tidal volume, with BALF and mRNA expression levels not significantly differing from the control. Zinc- and copper-containing welding fume particles adversely affect IPLs when instilled, as evidenced by the fatal loss in tidal volume and increased cytokine expression and secretion. The effects are mainly caused by the particles, not by the soluble fraction. Full article

(This article belongs to the Special Issue Myeloperoxidase)

► Show Figures

Figure 1

21 pages, 4867 KiB

Open AccessArticle

Myeloperoxidase as a Marker to Differentiate Mouse Monocyte/Macrophage Subsets

by Cody J. Gurski and Bonnie N. Dittel

Int. J. Mol. Sci. 2022, 23(15), 8246; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23158246 - 26 Jul 2022

Cited by 8 | Viewed by 4748

Abstract

Macrophages are present in every tissue in the body and play essential roles in homeostasis and host defense against microorganisms. Some tissue macrophages derive from the yolk sac/fetal liver that populate tissues for life. Other tissue macrophages derive from monocytes that differentiate in the bone marrow and circulate through tissues via the blood and lymphatics. Circulating monocytes are very plastic and differentiate into macrophages with specialized functions upon entering tissues. Specialized monocyte/macrophage subsets have been difficult to differentiate based on cell surface markers. Here, using a combination of “pan” monocyte/macrophage markers and flow cytometry, we asked whether myeloperoxidase (MPO) could be used as a marker of pro-inflammatory monocyte/macrophage subsets. MPO is of interest because of its potent microbicidal activity. In wild-type SPF housed mice, we found that MPO⁺ monocytes/macrophages were present in peripheral blood, spleen, small and large intestines, and mesenteric lymph nodes, but not the central nervous system. Only monocytes/macrophages that expressed cell surface F4/80 and/or Ly6C co-expressed MPO with the highest expression in F4/80^HiLy6C^Hi subsets regardless of tissue. These cumulative data indicate that MPO expression can be used as an additional marker to differentiate between monocyte/macrophage subsets with pro-inflammatory and microbicidal activity in a variety of tissues. Full article

(This article belongs to the Special Issue Myeloperoxidase)

► Show Figures

Figure 1

Review

Jump to: Research

17 pages, 807 KiB

Open AccessReview

Non-Canonical Functions of Myeloperoxidase in Immune Regulation, Tissue Inflammation and Cancer

by Joey S. Lockhart and Ronen Sumagin

Int. J. Mol. Sci. 2022, 23(20), 12250; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232012250 - 14 Oct 2022

Cited by 8 | Viewed by 3583

Abstract

Myeloperoxidase (MPO) is one of the most abundantly expressed proteins in neutrophils. It serves as a critical component of the antimicrobial defense system, facilitating microbial killing via generation of reactive oxygen species (ROS). Interestingly, emerging evidence indicates that in addition to the well-recognized canonical antimicrobial function of MPO, it can directly or indirectly impact immune cells and tissue responses in homeostatic and disease states. Here, we highlight the emerging non-canonical functions of MPO, including its impact on neutrophil longevity, activation and trafficking in inflammation, its interactions with other immune cells, and how these interactions shape disease outcomes. We further discuss MPO interactions with barrier forming endothelial and epithelial cells, specialized cells of the central nervous system (CNS) and its involvement in cancer progression. Such diverse function and the MPO association with numerous inflammatory disorders make it an attractive target for therapies aimed at resolving inflammation and limiting inflammation-associated tissue damage. However, while considering MPO inhibition as a potential therapy, one must account for the diverse impact of MPO activity on various cellular compartments both in health and disease. Full article

(This article belongs to the Special Issue Myeloperoxidase)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Myeloperoxidase

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (7 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI